Mechanisms of DNA–protein crosslink repair (original) (raw)

• Lindahl, T. Instability and decay of the primary structure of DNA. Nature 362, 709–715 (1993).
  CAS PubMed Google Scholar
• Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 1071–1078 (2009).
  CAS PubMed PubMed Central Google Scholar
• Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
  CAS PubMed Google Scholar
• Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).
  Article CAS PubMed Google Scholar
• Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).
  Article CAS PubMed Google Scholar
• Oza, A. M. et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 16, 87–97 (2015).
  Article CAS PubMed Google Scholar
• Nakano, T. et al. T7 RNA polymerases backed up by covalently trapped proteins catalyze highly error prone transcription. J. Biol. Chem. 287, 6562–6572 (2012).
  Article CAS PubMed Google Scholar
• Nakano, T. et al. Translocation and stability of replicative DNA helicases upon encountering DNA-protein cross-links. J. Biol. Chem. 288, 4649–4658 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Fu, Y. V. et al. Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell 146, 931–941 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Kuo, H. K., Griffith, J. D. & Kreuzer, K. N. 5-Azacytidine induced methyltransferase-DNA adducts block DNA replication in vivo. Cancer Res. 67, 8248–8254 (2007).
  Article CAS PubMed Google Scholar
• Stingele, J. & Jentsch, S. DNA-protein crosslink repair. Nat. Rev. Mol. Cell Biol. 16, 455–460 (2015).
  Article CAS PubMed Google Scholar
• Chvalova, K., Brabec, V. & Kasparkova, J. Mechanism of the formation of DNA-protein cross-links by antitumor cisplatin. Nucleic Acids Res. 35, 1812–1821 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Pommier, Y. & Marchand, C. Interfacial inhibitors: targeting macromolecular complexes. Nat. Rev. Drug Discov. 11, 25–36 (2011).
  Article PubMed CAS PubMed Central Google Scholar
• Nitiss, J. L. Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer 9, 338–350 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Fenaux, P. et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 10, 223–232 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Fenaux, P. et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J. Clin. Oncol. 28, 562–569 (2010).
  Article CAS PubMed Google Scholar
• Maslov, A. Y. et al. 5-Aza-2′-deoxycytidine-induced genome rearrangements are mediated by DNMT1. Oncogene 31, 5172–5179 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• O'Connor, M. J. Targeting the DNA damage response in cancer. Mol. Cell 60, 547–560 (2015).
  Article CAS PubMed Google Scholar
• Mateo, J. et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373, 1697–1708 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Murai, J. et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 72, 5588–5599 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Barker, S., Weinfeld, M. & Murray, D. DNA-protein crosslinks: their induction, repair, and biological consequences. Mutat. Res. 589, 111–135 (2005).
  Article CAS PubMed Google Scholar
• Pommier, Y. et al. Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2). DNA Repair (Amst.) 19, 114–129 (2014).
  Article CAS Google Scholar
• DeMott, M. S. et al. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J. Biol. Chem. 277, 7637–7640 (2002).
  Article CAS PubMed Google Scholar
• Sczepanski, J. T., Wong, R. S., McKnight, J. N., Bowman, G. D. & Greenberg, M. M. Rapid DNA–protein cross-linking and strand scission by an abasic site in a nucleosome core particle. Proc. Natl Acad. Sci. USA 107, 22475–22480 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Shi, Y. et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941–953 (2004).
  Article CAS PubMed Google Scholar
• Yang, S. W. et al. A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. Proc. Natl Acad. Sci. USA 93, 11534–11539 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Pouliot, J. J., Yao, K. C., Robertson, C. A. & Nash, H. A. Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. Science 286, 552–555 (1999). References 26 and 27 identify Tdp1 in yeast as an enzyme that is capable of releasing covalent Top1 adducts.
  Article CAS PubMed Google Scholar
• Lin, C. P., Ban, Y., Lyu, Y. L., Desai, S. D. & Liu, L. F. A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes. J. Biol. Chem. 283, 21074–21083 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Interthal, H. & Champoux, J. J. Effects of DNA and protein size on substrate cleavage by human tyrosyl-DNA phosphodiesterase 1. Biochem. J. 436, 559 (2011).
  Article CAS PubMed Google Scholar
• Debethune, L., Kohlhagen, G., Grandas, A. & Pommier, Y. Processing of nucleopeptides mimicking the topoisomerase I-DNA covalent complex by tyrosyl-DNA phosphodiesterase. Nucleic Acids Res. 30, 1198–1204 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• El-Khamisy, S. F. To live or to die: a matter of processing damaged DNA termini in neurons. EMBO Mol. Med. 3, 78–88 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Hudson, J. J., Chiang, S. C., Wells, O. S., Rookyard, C. & El-Khamisy, S. F. SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. Nat. Commun. 3, 733 (2012).
  Article PubMed CAS Google Scholar
• Das, B. B. et al. PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage. Nucleic Acids Res. 42, 4435–4449 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Das, B. B. et al. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. EMBO J. 28, 3667–3680 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Chiang, S. C., Carroll, J. & El-Khamisy, S. F. TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle 9, 588–595 (2010).
  Article CAS PubMed Google Scholar
• Shiloh, Y. & Ziv, Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat. Rev. Mol. Cell Biol. 14, 197–210 (2013).
  Article CAS PubMed Google Scholar
• Cortes Ledesma, F., El Khamisy, S. F., Zuma, M. C., Osborn, K. & Caldecott, K. W. A human 5′-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage. Nature 461, 674–678 (2009). Identified TDP2 as the first-characterized human enzyme with 5′-tyrosyl DNA phosphodiesterase activity, which is important for releasing covalent TOP2 adducts.
  Article PubMed CAS Google Scholar
• Gao, R. et al. Proteolytic degradation of topoisomerase II (Top2) enables the processing of Top2·DNA and Top2·RNA covalent complexes by tyrosyl-DNA-phosphodiesterase 2 (TDP2). J. Biol. Chem. 289, 17960–17969 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Mao, Y., Desai, S. D., Ting, C. Y., Hwang, J. & Liu, L. F. 26 S proteasome-mediated degradation of topoisomerase II cleavable complexes. J. Biol. Chem. 276, 40652–40658 (2001).
  Article CAS PubMed Google Scholar
• Gomez-Herreros, F. et al. TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. Nat. Genet. 46, 516–521 (2014).
  Article CAS PubMed Google Scholar
• Gomez-Herreros, F. et al. TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genet. 9, e1003226 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Rao, T. et al. Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage. Nucleic Acids Res. 44, 10201–10215 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Stracker, T. H. & Petrini, J. H. The MRE11 complex: starting from the ends. Nat. Rev. Mol. Cell Biol. 12, 90–103 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Woodworth, D. L. & Kreuzer, K. N. Bacteriophage T4 mutants hypersensitive to an antitumor agent that induces topoisomerase-DNA cleavage complexes. Genetics 143, 1081–1090 (1996).
  CAS PubMed PubMed Central Google Scholar
• Stohr, B. A. & Kreuzer, K. N. Repair of topoisomerase-mediated DNA damage in bacteriophage T4. Genetics 158, 19–28 (2001).
  CAS PubMed PubMed Central Google Scholar
• Connelly, J. C., de Leau, E. S. & Leach, D. R. Nucleolytic processing of a protein-bound DNA end by the E. coli SbcCD (MR) complex. DNA Repair (Amst.) 2, 795–807 (2003).
  Article CAS Google Scholar
• Keeney, S., Giroux, C. N. & Kleckner, N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88, 375–384 (1997).
  Article CAS PubMed Google Scholar
• Neale, M. J., Pan, J. & Keeney, S. Endonucleolytic processing of covalent protein-linked DNA double-strand breaks. Nature 436, 1053–1057 (2005). Provides the first direct evidence that the nuclease MRN (MRX) can release covalent protein adducts from DSB ends.
  Article CAS PubMed PubMed Central Google Scholar
• Hartsuiker, E. et al. Ctp1CtIP and Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but Rec12Spo11 removal is dispensable for other MRN-dependent meiotic functions. Mol. Cell. Biol. 29, 1671–1681 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hartsuiker, E., Neale, M. J. & Carr, A. M. Distinct requirements for the Rad32Mre11 nuclease and Ctp1CtIP in the removal of covalently bound topoisomerase I and II from DNA. Mol. Cell 33, 117–123 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Malik, M. & Nitiss, J. L. DNA repair functions that control sensitivity to topoisomerase-targeting drugs. Eukaryot. Cell 3, 82–90 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, K. C. et al. MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA. Biol. Open 1, 863–873 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Hoa, N. N. et al. Mre11 is essential for the removal of lethal topoisomerase 2 covalent cleavage complexes. Mol. Cell 64, 580–592 (2016).
  Article CAS PubMed Google Scholar
• Aparicio, T., Baer, R., Gottesman, M. & Gautier, J. MRN, CtIP, and BRCA1 mediate repair of topoisomerase II-DNA adducts. J. Cell Biol. 212, 399–408 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Deshpande, R. A., Lee, J. H., Arora, S. & Paull, T. T. Nbs1 converts the human Mre11/Rad50 nuclease complex into an endo/exonuclease machine specific for protein-DNA adducts. Mol. Cell 64, 593–606 (2016).
  Article CAS PubMed Google Scholar
• Cannavo, E. & Cejka, P. Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50-Xrs2 to resect DNA breaks. Nature 514, 122–125 (2014).
  Article CAS PubMed Google Scholar
• Sartori, A. A. et al. Human CtIP promotes DNA end resection. Nature 450, 509–514 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Sacho, E. J. & Maizels, N. DNA repair factor MRE11/RAD50 cleaves 3′-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons. J. Biol. Chem. 286, 44945–44951 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• de Graaf, B., Clore, A. & McCullough, A. K. Cellular pathways for DNA repair and damage tolerance of formaldehyde-induced DNA-protein crosslinks. DNA Repair (Amst.) 8, 1207–1214 (2009).
  Article CAS Google Scholar
• Stingele, J., Schwarz, M. S., Bloemeke, N., Wolf, P. G. & Jentsch, S. A. DNA-dependent protease involved in DNA-protein crosslink repair. Cell 158, 327–338 (2014). Identifies Wss1 as a DNA-dependent protease that repairs covalent DPCs.
  Article CAS PubMed Google Scholar
• Duxin, J. P., Dewar, J. M., Yardimci, H. & Walter, J. C. Repair of a DNA-protein crosslink by replication-coupled proteolysis. Cell 159, 346–357 (2014). Describes the detailed mechanisms of replication-coupled proteolytic DPC repair.
  Article CAS PubMed PubMed Central Google Scholar
• Stingele, J. et al. Mechanism and regulation of DNA-protein crosslink repair by the DNA-dependent metalloprotease SPRTN. Mol. Cell 64, 688–703 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Vaz, B. et al. Metalloprotease SPRTN/DVC1 orchestrates replication-coupled DNA-protein crosslink repair. Mol. Cell 64, 704–719 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Lopez-Mosqueda, J. et al. SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks. eLife 5, e21491 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Morocz, M. et al. DNA-dependent protease activity of human Spartan facilitates replication of DNA-protein crosslink-containing DNA. Nucleic Acids Res. 45, 3172–3188 (2017).
  CAS PubMed PubMed Central Google Scholar
• Maskey, R. S. et al. Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis. Nucleic Acids Res. 45, 4564–4576 (2017). References 62–66 identify SPRTN as the DPC protease that operates in higher eukaryotes.
  Article CAS PubMed PubMed Central Google Scholar
• Stingele, J., Habermann, B. & Jentsch, S. DNA-protein crosslink repair: proteases as DNA repair enzymes. Trends Biochem. Sci. 40, 67–71 (2015).
  Article CAS PubMed Google Scholar
• Ruijs, M. W. G. et al. Atypical progeroid syndrome: an unknown helicase gene defect? Am. J. Med. Genet. A 116A, 295–299 (2003).
  Article CAS PubMed Google Scholar
• Lessel, D. et al. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. Nat. Genet. 46, 1239–1244 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Machida, Y., Kim, M. S. & Machida, Y. J. Spartan/C1orf124 is important to prevent UV-induced mutagenesis. Cell Cycle 11, 3395–3402 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Nakano, T. et al. Homologous recombination but not nucleotide excision repair plays a pivotal role in tolerance of DNA-protein cross-links in mammalian cells. J. Biol. Chem. 284, 27065–27076 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Nakano, T. et al. Nucleotide excision repair and homologous recombination systems commit differentially to the repair of DNA-protein crosslinks. Mol. Cell 28, 147–158 (2007).
  Article CAS PubMed Google Scholar
• Baker, D. J. et al. Nucleotide excision repair eliminates unique DNA-protein cross-links from mammalian cells. J. Biol. Chem. 282, 22592–22604 (2007).
  Article CAS PubMed Google Scholar
• Vance, J. R. & Wilson, T. E. Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage. Proc. Natl Acad. Sci. USA 99, 13669–13674 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, Y. W. et al. Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells. Nucleic Acids Res. 39, 3607–3620 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ridpath, J. R. et al. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde. Cancer Res. 67, 11117–11122 (2007).
  Article CAS PubMed Google Scholar
• Garaycoechea, J. I. et al. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function. Nature 489, 571–575 (2012).
  Article CAS PubMed Google Scholar
• Langevin, F., Crossan, G. P., Rosado, I. V., Arends, M. J. & Patel, K. J. Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice. Nature 475, 53–58 (2011).
  Article CAS PubMed Google Scholar
• Rosado, I. V., Langevin, F., Crossan, G. P., Takata, M. & Patel, K. J. Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway. Nat. Struct. Mol. Biol. 18, 1432–1434 (2011).
  Article CAS PubMed Google Scholar
• Kottemann, M. C. & Smogorzewska, A. Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493, 356–363 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Duxin, J. P. & Walter, J. C. What is the DNA repair defect underlying Fanconi anemia? Curr. Opin. Cell Biol. 37, 49–60 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Orta, M. L. et al. 5-Aza-2′-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair. Nucleic Acids Res. 41, 5827–5836 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Deng, C., Brown, J. A., You, D. & Brown, J. M. Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae. Genetics 170, 591–600 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Delabaere, L. et al. The Spartan ortholog maternal haploid is required for paternal chromosome integrity in the Drosophila zygote. Curr. Biol. 24, 2281–2287 (2014).
  Article CAS PubMed Google Scholar
• Huang, S. N., Pommier, Y. & Marchand, C. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitors. Expert Opin. Ther. Pat. 21, 1285–1292 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Takemura, H. et al. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks. J. Biol. Chem. 281, 30814–30823 (2006).
  Article CAS PubMed Google Scholar
• Giannini, G. et al. Mutations of an intronic repeat induce impaired MRE11 expression in primary human cancer with microsatellite instability. Oncogene 23, 2640–2647 (2004).
  Article CAS PubMed Google Scholar
• Raoof, A. et al. Toxoflavins and deazaflavins as the first reported selective small molecule inhibitors of tyrosyl-DNA phosphodiesterase II. J. Med. Chem. 56, 6352–6370 (2013).
  Article CAS PubMed Google Scholar
• Dupre, A. et al. A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex. Nat. Chem. Biol. 4, 119–125 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Shibata, A. et al. DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol. Cell 53, 7–18 (2014).
  Article CAS PubMed Google Scholar
• Takashima, H. et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat. Genet. 32, 267–272 (2002).
  Article CAS PubMed Google Scholar
• Interthal, H. et al. SCAN1 mutant Tdp1 accumulates the enzyme—DNA intermediate and causes camptothecin hypersensitivity. EMBO J. 24, 2224–2233 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Hernandez, D. et al. A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11q22-23. J. Med. Genet. 30, 135–140 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Stewart, G. S. et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99, 577–587 (1999).
  Article CAS PubMed Google Scholar
• Saar, K. et al. The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21. Am. J. Hum. Genet. 60, 605–610 (1997).
  CAS PubMed PubMed Central Google Scholar
• Varon, R. et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93, 467–476 (1998).
  Article CAS PubMed Google Scholar
• Weemaes, C. M. et al. A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr. Scand. 70, 557–564 (1981).
  Article CAS PubMed Google Scholar
• Carney, J. P. et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93, 477–486 (1998).
  Article CAS PubMed Google Scholar
• Chrzanowska, K. H., Gregorek, H., Dembowska-Baginska, B., Kalina, M. A. & Digweed, M. Nijmegen breakage syndrome (NBS). Orphanet J. Rare Dis. 7, 13 (2012).
  Article PubMed PubMed Central Google Scholar
• Waltes, R. et al. Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am. J. Hum. Genet. 84, 605–616 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Barbi, G. et al. Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child. Am. J. Med. Genet. 40, 44–50 (1991).
  Article CAS PubMed Google Scholar