Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology (original) (raw)
Abou Jamra R, Philippe O, Raas-Rothschild A et al (2011) Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet 88:788–795. doi:10.1016/j.ajhg.2011.04.019 PubMed CentralCASPubMed Google Scholar
Ajit Bolar N, Vanlander AV, Wilbrecht C et al (2013) Mutation of the iron-sulfur cluster assembly gene IBA57 cause severe myopathy and encephalopathy. Hum Mol Genet 22:2590–2602 CASPubMed Google Scholar
Al-Saif A, Bohlega S, Al-Mohanna F (2012) Loss of ERLIN2 function leads to juvenile primary lateral sclerosis. Ann Neurol 72:510–516. doi:10.1002/ana.23641 CASPubMed Google Scholar
Anheim M, Lagier-Tourenne C, Stevanin G et al (2009) SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. J Neurol 256:104–108. doi:10.1007/s00415-009-0083-3 PubMed Google Scholar
Arnoldi A, Crimella C, Tenderini E et al (2012) Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations. Clin Genet 81(2):150–157. doi:10.1111/j.1399-0004.2011.01624.x CASPubMed Google Scholar
Atorino L, Silvestri L, Koppen M et al (2003) Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia. J Cell Biol 163:777–787. doi:10.1083/jcb.200304112 PubMed CentralCASPubMed Google Scholar
Barbosa MD, Barrat FJ, Tchernev VT et al (1997) Identification of mutations in two major mRNA isoforms of the Chediak–Higashi syndrome gene in human and mouse. Hum Mol Genet 6:1091–1098 PubMed CentralCASPubMed Google Scholar
Bauer P, Leshinsky-Silver E, Blumkin L et al (2012) Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47). Neurogenetics 13:73–76. doi:10.1007/s10048-012-0314-0 CASPubMed Google Scholar
Beetz C, Schüle R, Deconinck T et al (2008) REEP1 mutation spectrum and genotype/phenotype correlation in hereditary spastic paraplegia type 31. Brain 131:1078–1086. doi:10.1093/brain/awn026 PubMed CentralPubMed Google Scholar
Beetz C, Johnson A, Schuh AL et al (2013) Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure. Proc Natl Acad Sci 110:5091–5096. doi:10.1073/pnas.1217197110 PubMed CentralCASPubMed Google Scholar
Bettencourt C, Morris HR, Singleton AB et al (2013) Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to l-DOPA treatment. J Neurol 260:2414–2416. doi:10.1007/s00415-013-7044-6 PubMed CentralPubMed Google Scholar
Blumen SC, Bevan S, Abu-Mouch S et al (2003) A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24-q32. Ann Neurol 54:796–803. doi:10.1002/ana.10768 PubMed Google Scholar
Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F (2011) Autosomal recessive spastic ataxia of Charlevoix-Saguenay: an overview. Parkinsonism Relat Disord 17:418–422. doi:10.1016/j.parkreldis.2011.03.005 PubMed Google Scholar
Bouhouche A, Benomar A, Bouslam N et al (2006) Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J Med Genet 43:441–443. doi:10.1136/jmg.2005.039230 PubMed CentralCASPubMed Google Scholar
Boukhris A, Stevanin G, Feki I et al (2009) Tunisian hereditary spastic paraplegias: clinical variability supported by genetic heterogeneity. Clin Genet 75(6):527–536. doi:10.1111/j.1399-0004.2009.01176.x CASPubMed Google Scholar
Bross P, Naundrup S, Hansen J et al (2008) The Hsp60-(p. V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo. J Biol Chem 283:15694–15700. doi:10.1074/jbc.M800548200 PubMed CentralCASPubMed Google Scholar
Caballero Oteyza A, Battaloğlu E, Ocek L et al (2014) Motor protein mutations cause a new form of hereditary spastic paraplegia. Neurology 82(22):2007–2016. doi:10.1212/WNL.0000000000000479 CASPubMed Google Scholar
Casari G, De Fusco M, Ciarmatori S et al (1998) Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93:973–983 CASPubMed Google Scholar
Chang J, Lee S, Blackstone C (2014) Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest. 124(12):5249–5262. doi:10.1172/JCI77598 PubMed CentralPubMed Google Scholar
Citterio A, Arnoldi A, Panzeri E et al (2014) Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis. J Neurol 261(2):373–381. doi:10.1007/s00415-013-7206-6 CASPubMed Google Scholar
Cohen NR, Taylor JS, Scott LB et al (1998) Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol 8:26–33 CASPubMed Google Scholar
Collongues N, Depienne C, Boehm N et al (2013) Novel SPG10 mutation associated with dysautonomia, spinal cord atrophy, and skin biopsy abnormality. Eur J Neurol 20:398–401. doi:10.1111/j.1468-1331.2012.03803.x CASPubMed Google Scholar
Corona P, Lamantea E, Greco M et al (2002) Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. Ann Neurol 51:118–122. doi:10.1002/ana.10059 CASPubMed Google Scholar
Coutinho P, Barros J, Zemmouri R et al (1999) Clinical heterogeneity of autosomal recessive spastic paraplegias: analysis of 106 patients in 46 families. Arch Neurol 56:943–949 CASPubMed Google Scholar
Cremers FP, Pfeiffer RA, van de Pol TJ et al (1987) An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region. Hum Genet 77:23–27 CASPubMed Google Scholar
Crimella C, Baschirotto C, Arnoldi A et al (2012) Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-Tooth type 2. Clin Genet 82:157–164. doi:10.1111/j.1399-0004.2011.01717.x CASPubMed Google Scholar
Crow YJ, Zaki MS, Abdel-Hamid MS et al (2014) Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. Neuropediatrics 45(6):386–393. doi:10.1055/s-0034-1389161 CASPubMed Google Scholar
D’Amico A, Tessa A, Sabino A et al (2004) Incomplete penetrance in an SPG3A-linked family with a new mutation in the atlastin gene. Neurology 62:2138–2139 PubMed Google Scholar
Dan P, Edvardson S, Bielawski J, Hama H, Saada A (2011) 2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase. Lipids Health Dis 10:84. doi:10.1186/1476-511X-10-84 PubMed CentralCASPubMed Google Scholar
De Bot ST, Schelhaas HJ, Kamsteeg E-J, van de Warrenburg BPC (2012) Hereditary spastic paraplegia caused by a mutation in the VCP gene. Brain J Neurol 135:e223; author reply e224. doi:10.1093/brain/aws201 Google Scholar
Deniziak MA, Barciszewski J (2001) Methionyl-tRNA synthetase. Acta Biochim Pol 48:337–350 CASPubMed Google Scholar
Denton KR, Lei L, Grenier J, Rodionov V, Blackstone C, Li XJ (2014) Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia. Stem Cells 32(2):414–423. doi:10.1002/stem.1569 PubMed CentralCASPubMed Google Scholar
Depienne C, Tallaksen C, Lephay JY et al (2006) Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. J Med Genet 43:259–265. doi:10.1136/jmg.2005.035311 PubMed CentralCASPubMed Google Scholar
Dick KJ, Eckhardt M, Paisán-Ruiz C et al (2010) Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). Hum Mutat 31:E1251–E1260. doi:10.1002/humu.21205 CASPubMed Google Scholar
Dor T, Cinnamon Y, Raymond L et al (2014) KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. J Med Genet 51:137–142. doi:10.1136/jmedgenet-2013-102012 PubMed Google Scholar
Dumitrescu AM, Liao X-H, Best TB et al (2004) A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 74:168–175. doi:10.1086/380999 PubMed CentralCASPubMed Google Scholar
Dursun U, Koroglu C, Kocasoy Orhan E et al (2009) Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3-q25.1. Neurogenetics 10:325–331. doi:10.1007/s10048-009-0191-3 PubMed Google Scholar
Ebbing B, Mann K, Starosta A et al (2008) Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum Mol Genet 17:1245–1252. doi:10.1093/hmg/ddn014 CASPubMed Google Scholar
Edgar JM, McLaughlin M, Yool D et al (2004) Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J Cell Biol 166:121–131. doi:10.1083/jcb.200312012 PubMed CentralCASPubMed Google Scholar
Edvardson S, Hama H, Shaag A et al (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am J Hum Genet 83:643–648. doi:10.1016/j.ajhg.2008.10.010 PubMed CentralCASPubMed Google Scholar
Elliott AM, Simard LR, Coghlan G et al (2013) A novel mutation in KIAA0196: identification of a gene involved in Ritscher-Schinzel/3C syndrome in a First Nations cohort. J Med Genet 50:819–822. doi:10.1136/jmedgenet-2013-101715 CASPubMed Google Scholar
Engert JC, Bérubé P, Mercier J et al (2000) ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet 24:120–125. doi:10.1038/72769 CASPubMed Google Scholar
Erichsen AK, Koht J, Stray-Pedersen A et al (2009) Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study. Brain 132:1577–1588. doi:10.1093/brain/awp056 PubMed Google Scholar
Erlich Y, Edvardson S, Hodges E et al (2011) Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res 21:658–664. doi:10.1101/gr.117143.110 PubMed CentralCASPubMed Google Scholar
Falk J, Bonnon C, Girault J-A, Faivre-Sarrailh C (2002) F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination. Biol Cell 94:327–334 CASPubMed Google Scholar
Falk J, Rohde M, Bekhite MM et al (2014) Functional mutation analysis provides evidence for a role of REEP1 in lipid droplet biology. Hum Mutat 35:497–504. doi:10.1002/humu.22521 CASPubMed Google Scholar
Fassier C, Tarrade A, Peris L et al (2013) Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech 6:72–83. doi:10.1242/dmm.008946 PubMed CentralCASPubMed Google Scholar
Ferreirinha F, Quattrini A, Pirozzi M et al (2004) Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J Clin Invest 113:231–242. doi:10.1172/JCI20138 PubMed CentralCASPubMed Google Scholar
Fink JK (2003) The hereditary spastic paraplegias: nine genes and counting. Arch Neurol 60(8):1045–1049 PubMed Google Scholar
Finsterer J, Löscher W, Quasthoff S et al (2012) Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. J Neurol Sci 318:1–18. doi:10.1016/j.jns.2012.03.025 PubMed Google Scholar
Füger P, Sreekumar V, Schüle R et al (2012) Spastic paraplegia mutation N256S in the neuronal microtubule motor KIF5A disrupts axonal transport in a Drosophila HSP model. PLoS Genet 8:e1003066. doi:10.1371/journal.pgen.1003066 PubMed CentralPubMed Google Scholar
Furukawa Y, Graf WD, Wong H et al (2001) Dopa-responsive dystonia simulating spastic paraplegia due to tyrosine hydroxylase (TH) gene mutations. Neurology 56:260–263 CASPubMed Google Scholar
Ginsberg D, Cruz F, Herschorn S et al (2013) OnabotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity [corrected] regardless of concomitant anticholinergic use or neurologic etiology. Adv Ther 30:819–833. doi:10.1007/s12325-013-0054-z PubMed CentralCASPubMed Google Scholar
Goizet C, Boukhris A, Maltete D et al (2009a) SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum. Neurology 73:1111–1119. doi:10.1212/WNL.0b013e3181bacf59 CASPubMed Google Scholar
Goizet C, Boukhris A, Mundwiller E et al (2009b) Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Hum Mutat 30:E376–E385. doi:10.1002/humu.20920 PubMed Google Scholar
Goizet C, Depienne C, Benard G et al (2011) REEP1 mutations in SPG31: frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction. Hum Mutat 32:1118–1127. doi:10.1002/humu.21542 CASPubMed Google Scholar
Gonzalez M, McLaughlin H, Houlden H et al (2013) Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2. J Neurol Neurosurg Psychiatry 84:1247–1249. doi:10.1136/jnnp-2013-305049 PubMed CentralPubMed Google Scholar
Gonzalez-Carmona MA, Sandhoff R, Tacke F et al (2012) Beta-glucosidase 2 knockout mice with increased glucosylceramide show impaired liver regeneration. Liver Int 32:1354–1362. doi:10.1111/j.1478-3231.2012.02841.x CASPubMed Google Scholar
Hamdan FF, Gauthier J, Araki Y et al (2011) Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 88:306–316. doi:10.1016/j.ajhg.2011.02.001 PubMed CentralCASPubMed Google Scholar
Hansen JJ, Dürr A, Cournu-Rebeix I et al (2002) Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet 70:1328–1332. doi:10.1086/339935 PubMed CentralCASPubMed Google Scholar
Harding AE (1983) Classification of the hereditary ataxias and paraplegias. Lancet 1:1151–1155 CASPubMed Google Scholar
Hartig MB, Iuso A, Haack T et al (2011) Absence of an orphan mitochondrial protein, C19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet 89:543–550. doi:10.1016/j.ajhg.2011.09.007 PubMed CentralCASPubMed Google Scholar
Hanein S, Durr A, Ribai P et al (2007) A novel locus for autosomal dominant “uncomplicated” hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3. Hum Genet 122:261–273 CASPubMed Google Scholar
Hanein S, Martin E, Boukhris A et al (2008) Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal recessive spastic paraplegia including Kjellin syndrome. Am J Hum Genet 82:992–1002 PubMed CentralCASPubMed Google Scholar
Hazan J, Fonknechten N, Mavel D et al (1999) Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet 23:296–303. doi:10.1038/15472 CASPubMed Google Scholar
Heffernan LF, Simpson JC (2014) The trials and tubule-ations of Rab6 involvement in Golgi-to-ER retrograde transport. Biochem Soc Trans 42:1453–1459. doi:10.1042/BST20140178 CASPubMed Google Scholar
Hehr U, Bauer P, Winner B et al (2007) Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol 62:656–665. doi:10.1002/ana.21310 CASPubMed Google Scholar
Hewamadduma C, McDermott C, Kirby J et al (2009) New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP). Neurogenetics 10:105–110. doi:10.1007/s10048-008-0163-z CASPubMed Google Scholar
Hodgkinson CA, Bohlega S, Abu-Amero SN et al (2002) A novel form of autosomal recessive pure hereditary spastic paraplegia maps to chromosome 13q14. Neurology 59:1905–1909 CASPubMed Google Scholar
Ilgaz-Aydinlar E, Rolfs A, Serteser M, Parman Y (2014) Mutation in FAM134B causing hereditary sensory neuropathy with spasticity in a Turkish family. Muscle Nerve 49:774–775. doi:10.1002/mus.24145 PubMed Google Scholar
Jouet M, Rosenthal A, Armstrong G et al (1994) X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet 7:402–407. doi:10.1038/ng0794-402 CASPubMed Google Scholar
Kasher PR, De Vos KJ, Wharton SB et al (2009) Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem 110:34–44. doi:10.1111/j.1471-4159.2009.06104.x CASPubMed Google Scholar
Khan TN, Klar J, Tariq M et al (2014) Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation. Eur J Hum Genet 22(10):1180–1184. doi:10.1038/ejhg.2014.5 CASPubMed Google Scholar
Klebe S, Lossos A, Azzedine H et al (2012b) KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Eur J Hum Genet 20:645–649. doi:10.1038/ejhg.2011.261 PubMed CentralCASPubMed Google Scholar
Kruer MC, Paisán-Ruiz C, Boddaert N et al (2010) Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). Ann Neurol 68:611–618. doi:10.1002/ana.22122 CASPubMed Google Scholar
Kurth I, Pamminger T, Hennings JC et al (2009) Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat Genet 41:1179–1181. doi:10.1038/ng.464 CASPubMed Google Scholar
Landouré G, Zhu P-P, Lourenço CM et al (2013) Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. Hum Mutat 34:1357–1360. doi:10.1002/humu.22378 PubMed Google Scholar
Liguori R, Giannoccaro MP, Arnoldi A et al (2014) Impairment of brain and muscle energy metabolism detected by magnetic resonance spectroscopy in hereditary spastic paraparesis type 28 patients with DDHD1 mutations. J Neurol 261(9):1789–1793. doi:10.1007/s00415-014-7418-4 CASPubMed Google Scholar
Lin P, Li J, Liu Q et al (2008) A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42). Am J Hum Genet 83:752–759. doi:10.1016/j.ajhg.2008.11.003 PubMed CentralCASPubMed Google Scholar
Lindsey JC, Lusher ME, McDermott CJ et al (2000) Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. J Med Genet 37(10):759–765 PubMed CentralCASPubMed Google Scholar
Lossos A, Stümpfig C, Stevanin G et al (2015) Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology 84(7):659–667. doi:10.1212/WNL.0000000000001270 CASPubMed Google Scholar
Loureiro JL, Brandão E, Ruano L et al (2013) Autosomal dominant spastic paraplegias: a review of 89 families resulting from a Portuguese survey. JAMA Neurol 70:481–487. doi:10.1001/jamaneurol.2013.1956 PubMed Google Scholar
Luo Y, Chen C, Zhan Z et al (2014) Mutation and clinical characteristics of autosomal-dominant hereditary spastic paraplegias in china. Neurodegener Dis 14(4):176–183. doi:10.1159/000365513 PubMed Google Scholar
Macedo-Souza LI, Kok F, Santos S et al (2008) Reevaluation of a large family defines a new locus for X-linked recessive pure spastic paraplegia (SPG34) on chromosome Xq25. Neurogenetics 9:225–226. doi:10.1007/s10048-008-0130-8 PubMed Google Scholar
Magen D, Georgopoulos C, Bross P et al (2008) Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet 83:30–42. doi:10.1016/j.ajhg.2008.05.016 PubMed CentralCASPubMed Google Scholar
Magré J, Delépine M, Khallouf E et al (2001) Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet 28:365–370. doi:10.1038/ng585 PubMed Google Scholar
Mannan AU, Krawen P, Sauter SM et al (2006) ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia. Am J Hum Genet 79:351–357. doi:10.1086/504927 PubMed CentralCASPubMed Google Scholar
McDermott CJ, Dayaratne RK, Tomkins J et al (2001) Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England. Neurology 56(4):467–471 CASPubMed Google Scholar
Meijer IA, Hand CK, Cossette P et al (2002) Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia. Arch Neurol 59:281–286 PubMed Google Scholar
Meijer IA, Cossette P, Roussel J et al (2004) A novel locus for pure recessive hereditary spastic paraplegia maps to 10q22.1-10q24.1. Ann Neurol 56:579–582. doi:10.1002/ana.20239 CASPubMed Google Scholar
Mitne-Neto M, Kok F, Beetz C et al (2007) A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree. Eur J Hum Genet 15(12):1276–1279 CASPubMed Google Scholar
Montenegro G, Rebelo AP, Connell J et al (2012) Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. J Clin Invest 122:538–544. doi:10.1172/JCI60560 PubMed CentralCASPubMed Google Scholar
Moreno-De-Luca A, Helmers SL, Mao H et al (2011) Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. J Med Genet 48:141–144. doi:10.1136/jmg.2010.082263 PubMed CentralCASPubMed Google Scholar
Murakami Y, Tawamie H, Maeda Y et al (2014) Null mutation in PGAP1 impairing Gpi-anchor maturation in patients with intellectual disability and encephalopathy. PLoS Genet 10:e1004320. doi:10.1371/journal.pgen.1004320 PubMed CentralPubMed Google Scholar
Musumeci O, Bassi MT, Mazzeo A et al (2011) A novel mutation in KIF5A gene causing hereditary spastic paraplegia with axonal neuropathy. Neurol Sci 32:665–668. doi:10.1007/s10072-010-0445-8 PubMed Google Scholar
Neveling K, Martinez-Carrera LA, Hölker I et al (2013) Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy. Am J Hum Genet 92:946–954. doi:10.1016/j.ajhg.2013.04.011 PubMed CentralCASPubMed Google Scholar
Ohmi Y, Tajima O, Ohkawa Y et al (2011) Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: elucidation by a series of ganglioside-deficient mutant mice. J Neurochem 116:926–935. doi:10.1111/j.1471-4159.2010.07067.x CASPubMed Google Scholar
Orlacchio A, Kawarai T, Gaudiello F et al (2005) New locus for hereditary spastic paraplegia maps to chromosome 1p31.1-1p21.1. Ann Neurol 58:423–429. doi:10.1002/ana.20590 CASPubMed Google Scholar
Orlacchio A, Patrono C, Gaudiello F et al (2008) Silver syndrome variant of hereditary spastic paraplegia: a locus to 4p and allelism with SPG4. Neurology 70:1959–1966. doi:10.1212/01.wnl.0000294330.27058.61 CASPubMed Google Scholar
Orso G, Pendin D, Liu S et al (2009) Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin. Nature 460:978–983. doi:10.1038/nature08280 CASPubMed Google Scholar
Park SH, Zhu P-P, Parker RL, Blackstone C (2010) Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest 120:1097–1110. doi:10.1172/JCI40979 PubMed CentralCASPubMed Google Scholar
Patel H, Cross H, Proukakis C et al (2002) SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet 31:347–348. doi:10.1038/ng937 CASPubMed Google Scholar
Pérez-Brangulí F, Mishra HK, Prots I et al (2014) Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Hum Mol Genet 23:4859–4874. doi:10.1093/hmg/ddu200 PubMed CentralPubMed Google Scholar
Pfeffer G, Gorman GS, Griffin H et al (2014) Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain 137:1323–1336. doi:10.1093/brain/awu060 PubMed CentralPubMed Google Scholar
Proukakis C, Moore D, Labrum R, Wood NW, Houlden H (2011) Detection of novel mutations and review of published data suggests that hereditary spastic paraplegia caused by spastin (SPAST) mutations is found more often in males. J Neurol Sci 306(1–2):62–65. doi:10.1016/j.jns.2011.03.043 CASPubMed Google Scholar
Rahman M, Haberman A, Tracy C et al (2012) Drosophila mauve mutants reveal a role of LYST homologs late in the maturation of phagosomes and autophagosomes. Traffic 13:1680–1692. doi:10.1111/tra.12005 PubMed CentralCASPubMed Google Scholar
Rainier S, Chai J-H, Tokarz D et al (2003) NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet 73:967–971. doi:10.1086/378817 PubMed CentralCASPubMed Google Scholar
Reid E, Dearlove AM, Osborn O et al (2000) A locus for autosomal dominant “pure” hereditary spastic paraplegia maps to chromosome 19q13. Am J Hum Genet 66:728–732 PubMed CentralCASPubMed Google Scholar
Reid E, Kloos M, Ashley-Koch A et al (2002) A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet 71:1189–1194. doi:10.1086/344210 PubMed CentralCASPubMed Google Scholar
Renvoisé B, Stadler J, Singh R et al (2012) Spg20−/− mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling. Hum Mol Genet 21:3604–3618. doi:10.1093/hmg/dds191 PubMed CentralPubMed Google Scholar
Ribai P, Stevanin G, Bouslam N et al (2006) A new phenotype linked to SPG27 and refinement of the critical region on chromosome. J Neurol 253:714–719. doi:10.1007/s00415-006-0094-2 PubMed Google Scholar
Rivière J-B, Ramalingam S, Lavastre V et al (2011) KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet 89:219–230. doi:10.1016/j.ajhg.2011.06.013 PubMed CentralPubMed Google Scholar
Romagnolo A, Masera S, Mattioda A et al (2014) Atypical hereditary spastic paraplegia mimicking multiple sclerosis associated with a novel SPG11 mutation. Eur J Neurol 21:e14–e15. doi:10.1111/ene.12297 CASPubMed Google Scholar
Rosenthal A, Jouet M, Kenwrick S (1992) Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nat Genet 2:107–112. doi:10.1038/ng1092-107 CASPubMed Google Scholar
Ruano L, Melo C, Silva MC, Coutinho P (2014) The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42:174–183. doi:10.1159/000358801 PubMed Google Scholar
Sánchez-Ferrero E, Coto E, Beetz C et al (2013) SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p. A510V. Clin Genet 83(3):257–262. doi:10.1111/j.1399-0004.2012.01896.x PubMed Google Scholar
Saugier-Veber P, Munnich A, Bonneau D et al (1994) X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus. Nat Genet 6:257–262. doi:10.1038/ng0394-257 CASPubMed Google Scholar
Schneider SA, Bhatia KP (2010) Three faces of the same gene: FA2H links neurodegeneration with brain iron accumulation, leukodystrophies, and hereditary spastic paraplegias. Ann Neurol 68:575–577. doi:10.1002/ana.22211 CASPubMed Google Scholar
Schüle R, Bonin M, Dürr A et al (2009a) Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24. Neurology 72:1893–1898. doi:10.1212/WNL.0b013e3181a6086c PubMed Google Scholar
Schüle R, Schlipf N, Synofzik M et al (2009b) Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry 80:1402–1404. doi:10.1136/jnnp.2008.167528 PubMed Google Scholar
Schüle R, Siddique T, Deng H-X et al (2010) Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis. J Lipid Res 51:819–823. doi:10.1194/jlr.M002543 PubMed CentralPubMed Google Scholar
Schuurs-Hoeijmakers JHM, Geraghty MT, Kamsteeg E-J et al (2012) Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia. Am J Hum Genet 91:1073–1081. doi:10.1016/j.ajhg.2012.10.017 PubMed CentralCASPubMed Google Scholar
Schwartz CE, May MM, Carpenter NJ et al (2005) Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet 77:41–53. doi:10.1086/431313 PubMed CentralCASPubMed Google Scholar
Sedel F, Fontaine B, Saudubray JM, Lyon-Caen O (2007) Hereditary spastic paraparesis in adults associated with inborn errors of metabolism: a diagnostic approach. J Inherit Metab Dis 30:855–864. doi:10.1007/s10545-007-0745-1 CASPubMed Google Scholar
Seri M, Cusano R, Forabosco P et al (1999) Genetic mapping to 10q23.3-q24.2, in a large Italian pedigree, of a new syndrome showing bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy. Am J Hum Genet 64:586–593. doi:10.1086/302241 PubMed CentralCASPubMed Google Scholar
Shimazaki H, Takiyama Y, Ishiura H et al (2012) A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55). J Med Genet 49:777–784. doi:10.1136/jmedgenet-2012-101212 CASPubMed Google Scholar
Shimazaki H, Honda J, Naoi T et al (2014) Autosomal-recessive complicated spastic paraplegia with a novel lysosomal trafficking regulator gene mutation. J Neurol Neurosurg Psychiatry 85:1024–1028. doi:10.1136/jnnp-2013-306981 PubMed Google Scholar
Simpson MA, Cross H, Proukakis C et al (2003) Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia. Am J Hum Genet 73:1147–1156. doi:10.1086/379522 PubMed CentralCASPubMed Google Scholar
Sivakumar K, Sambuughin N, Selenge B et al (1999) Novel exon 3B proteolipid protein gene mutation causing late-onset spastic paraplegia type 2 with variable penetrance in female family members. Ann Neurol 45:680–683 CASPubMed Google Scholar
Słabicki M, Theis M, Krastev DB et al (2010) A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. PLoS Biol 8:e1000408. doi:10.1371/journal.pbio.1000408 PubMed CentralPubMed Google Scholar
Spiegel R, Mandel H, Saada A et al (2014) Delineation of C12orf65-related phenotypes: a genotype–phenotype relationship. Eur J Hum Genet 22:1019–1025. doi:10.1038/ejhg.2013.284 CASPubMed Google Scholar
Starling A, Rocco P, Passos-Bueno MR, Hazan J, Marie SK, Zatz M (2002) Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree. J Med Genet 39(12):e77 PubMed CentralCASPubMed Google Scholar
Steinmüller R, Lantigua-Cruz A, Garcia-Garcia R et al (1997) Evidence of a third locus in X-linked recessive spastic paraplegia. Hum Genet 100:287–289. doi:10.1007/s004390050507 PubMed Google Scholar
Stevanin G, Santorelli FM, Azzedine H et al (2007b) Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet 39:366–372. doi:10.1038/ng1980 CASPubMed Google Scholar
Stevanin G, Azzedine H, Denora P et al (2008a) Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain 131:772–784. doi:10.1093/brain/awm293 PubMed Google Scholar
Stevanin G, Ruberg M, Brice A (2008b) Recent advances in the genetics of spastic paraplegias. Curr Neurol Neurosci Rep 8:198–210 PubMed Google Scholar
Svenson IK, Kloos MT, Gaskell PC et al (2004) Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations. Neurogenetics 5:157–164. doi:10.1007/s10048-004-0186-z CASPubMed Google Scholar
Synofzik M, Gonzalez MA, Lourenco CM et al (2014) PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Brain 137:69–77. doi:10.1093/brain/awt326 PubMed CentralPubMed Google Scholar
Tanyel MC, Mancano LD (1997) Neurologic findings in vitamin E deficiency. Am Fam Physician 55:197–201 CASPubMed Google Scholar
Tarrade A, Fassier C, Courageot S et al (2006) A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet 15:3544–3558. doi:10.1093/hmg/ddl431 CASPubMed Google Scholar
Tessa A, Silvestri G, de Leva MF et al (2008) A novel KIF5A/SPG10 mutation in spastic paraplegia associated with axonal neuropathy. J Neurol 255:1090–1092. doi:10.1007/s00415-008-0840-8 CASPubMed Google Scholar
Tesson C, Nawara M, Salih MAM et al (2012) Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. Am J Hum Genet 91:1051–1064. doi:10.1016/j.ajhg.2012.11.001 PubMed CentralCASPubMed Google Scholar
Tiranti V, Corona P, Greco M et al (2000) A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome. Hum Mol Genet 9:2733–2742. doi:10.1093/hmg/9.18.2733 CASPubMed Google Scholar
Tsang HTH, Edwards TL, Wang X et al (2009) The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling. Hum Mol Genet 18:3805–3821. doi:10.1093/hmg/ddp324 PubMed CentralCASPubMed Google Scholar
Uhlenberg B, Schuelke M, Rüschendorf F et al (2004) Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus–Merzbacher-like disease. Am J Hum Genet 75:251–260. doi:10.1086/422763 PubMed CentralCASPubMed Google Scholar
Valdmanis PN, Meijer IA, Reynolds A et al (2007) Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia. Am J Hum Genet 80:152–161. doi:10.1086/510782 PubMed CentralCASPubMed Google Scholar
Valente EM, Brancati F, Caputo V et al (2002) Novel locus for autosomal dominant pure hereditary spastic paraplegia (SPG19) maps to chromosome 9q33-q34. Ann Neurol 51:681–685. doi:10.1002/ana.10204 CASPubMed Google Scholar
Varga R-E, Schüle R, Fadel H et al (2013) Do not trust the pedigree: reduced and sex-dependent penetrance at a novel mutation hotspot in ATL1 blurs autosomal dominant inheritance of spastic paraplegia. Hum Mutat 34:860–863. doi:10.1002/humu.22309 CASPubMed Google Scholar
Vazza G, Zortea M, Boaretto F et al (2000) A new locus for autosomal recessive spastic paraplegia associated with mental retardation and distal motor neuropathy, SPG14, maps to chromosome 3q27-q28. Am J Hum Genet 67:504–509. doi:10.1086/303017 PubMed CentralCASPubMed Google Scholar
Verny C, Guegen N, Desquiret V et al (2011) Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation. Mitochondrion 11:70–75. doi:10.1016/j.mito.2010.07.006 CASPubMed Google Scholar
Votsi C, Zamba-Papanicolaou E, Middleton LT et al (2014) A novel GBA2 gene missense mutation in spastic ataxia. Ann Hum Genet 78:13–22. doi:10.1111/ahg.12045 CASPubMed Google Scholar
Wakil SM, Bohlega S, Hagos S et al (2013) A novel splice site mutation in ERLIN2 causes hereditary spastic paraplegia in a Saudi family. Eur J Med Genet 56:43–45. doi:10.1016/j.ejmg.2012.10.003 PubMed Google Scholar
Wan J, Yourshaw M, Mamsa H et al (2012) Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet 44:704–708. doi:10.1038/ng.2254 PubMed CentralCASPubMed Google Scholar
Wang X, Shaw WR, Tsang HTH et al (2007) Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules. Nat Neurosci 10:177–185. doi:10.1038/nn1841 PubMed CentralCASPubMed Google Scholar
Wang X, Yang Y, Wang X, Li C, Jia J (2014) A novel KIAA0196 (SPG8) mutation in a Chinese family with spastic paraplegia. Chin Med J (Engl) 127(10):1987–1989 Google Scholar
Watts GDJ, Wymer J, Kovach MJ et al (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 36:377–381. doi:10.1038/ng1332 CASPubMed Google Scholar
Werner HB, Krämer-Albers E-M, Strenzke N et al (2013) A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system. Glia 61:567–586. doi:10.1002/glia.22456 PubMed Google Scholar
Windpassinger C, Auer-Grumbach M, Irobi J et al (2004) Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet 36:271–276. doi:10.1038/ng1313 CASPubMed Google Scholar
Yao D, McGonigal R, Barrie JA et al (2014) Neuronal expression of GalNAc transferase is sufficient to prevent the age-related neurodegenerative phenotype of complex ganglioside-deficient mice. J Neurosci 34:880–891. doi:10.1523/JNEUROSCI.3996-13.2014 PubMed CentralCASPubMed Google Scholar
Yıldırım Y, Orhan EK, Iseri SAU et al (2011) A frameshift mutation of ERLIN2 in recessive intellectual disability, motor dysfunction and multiple joint contractures. Hum Mol Genet 20:1886–1892. doi:10.1093/hmg/ddr070 PubMed Google Scholar
Zanni G, Scotton C, Passarelli C et al (2013) Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. Neurogenetics 14:247–250. doi:10.1007/s10048-013-0371-z CASPubMed Google Scholar
Zhao X, Alvarado D, Rainier S et al (2001) Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet 29:326–331. doi:10.1038/ng758 CASPubMed Google Scholar
Zhao G, Hu Z, Shen L et al (2008) A novel candidate locus on chromosome 11p14.1-p11.2 for autosomal dominant hereditary spastic paraplegia. Chin Med J (Engl) 121:430–434 CAS Google Scholar
Zhu P-P, Denton KR, Pierson TM et al (2014) Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A. Hum Mol Genet 23:5638–5648. doi:10.1093/hmg/ddu280 PubMed Google Scholar
Zivony-Elboum Y, Westbroek W, Kfir N et al (2012) A founder mutation in Vps37A causes autosomal recessive complex hereditary spastic paraparesis. J Med Genet 49:462–472. doi:10.1136/jmedgenet-2012-100742 CASPubMed Google Scholar
Zöller I, Meixner M, Hartmann D et al (2008) Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration. J Neurosci 28:9741–9754. doi:10.1523/JNEUROSCI.0458-08.2008 PubMed Google Scholar
Zortea M, Vettori A, Trevisan CP et al (2002) Genetic mapping of a susceptibility locus for disc herniation and spastic paraplegia on 6q23.3-q24.1. J Med Genet 39:387–390 PubMed CentralCASPubMed Google Scholar
Züchner S, Wang G, Tran-Viet K-N et al (2006) Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31. Am J Hum Genet 79:365–369. doi:10.1086/505361 PubMed CentralPubMed Google Scholar