The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps within the Smith-Magenis microdeletion critical region in 17p11.2 (original) (raw)

. 1995 Jan;56(1):175–182.

Abstract

The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed.

175

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bodmer W. F. The William Allan Memorial Award Address: Gene clusters, Genome organization, and complex phenotypes. When the sequence is known, what will it mean? Am J Hum Genet. 1981 Sep;33(5):664–682. [PMC free article] [PubMed] [Google Scholar]
  2. Bretscher A. Microfilament structure and function in the cortical cytoskeleton. Annu Rev Cell Biol. 1991;7:337–374. doi: 10.1146/annurev.cb.07.110191.002005. [DOI] [PubMed] [Google Scholar]
  3. Campbell H. D., Schimansky T., Claudianos C., Ozsarac N., Kasprzak A. B., Cotsell J. N., Young I. G., de Couet H. G., Miklos G. L. The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11386–11390. doi: 10.1073/pnas.90.23.11386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chance P. F., Abbas N., Lensch M. W., Pentao L., Roa B. B., Patel P. I., Lupski J. R. Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17. Hum Mol Genet. 1994 Feb;3(2):223–228. doi: 10.1093/hmg/3.2.223. [DOI] [PubMed] [Google Scholar]
  5. Chance P. F., Alderson M. K., Leppig K. A., Lensch M. W., Matsunami N., Smith B., Swanson P. D., Odelberg S. J., Disteche C. M., Bird T. D. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993 Jan 15;72(1):143–151. doi: 10.1016/0092-8674(93)90058-x. [DOI] [PubMed] [Google Scholar]
  6. Chevillard C., Le Paslier D., Passage E., Ougen P., Billault A., Boyer S., Mazan S., Bachellerie J. P., Vignal A., Cohen D. Relationship between Charcot-Marie-Tooth 1A and Smith-Magenis regions. snU3 may be a candidate gene for the Smith-Magenis syndrome. Hum Mol Genet. 1993 Aug;2(8):1235–1243. doi: 10.1093/hmg/2.8.1235. [DOI] [PubMed] [Google Scholar]
  7. Colley A. F., Leversha M. A., Voullaire L. E., Rogers J. G. Five cases demonstrating the distinctive behavioural features of chromosome deletion 17(p11.2 p11.2) (Smith-Magenis syndrome). J Paediatr Child Health. 1990 Feb;26(1):17–21. doi: 10.1111/j.1440-1754.1990.tb02372.x. [DOI] [PubMed] [Google Scholar]
  8. Elder F. F., Nichols M. M., Hood O. J., Harrison W. R., 3rd Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome. Am J Med Genet. 1985 Mar;20(3):519–524. doi: 10.1002/ajmg.1320200312. [DOI] [PubMed] [Google Scholar]
  9. Eldon E., Kooyer S., D'Evelyn D., Duman M., Lawinger P., Botas J., Bellen H. The Drosophila 18 wheeler is required for morphogenesis and has striking similarities to Toll. Development. 1994 Apr;120(4):885–899. doi: 10.1242/dev.120.4.885. [DOI] [PubMed] [Google Scholar]
  10. Evans G. A., Lewis K., Rothenberg B. E. High efficiency vectors for cosmid microcloning and genomic analysis. Gene. 1989 Jun 30;79(1):9–20. doi: 10.1016/0378-1119(89)90088-7. [DOI] [PubMed] [Google Scholar]
  11. Ewart A. K., Morris C. A., Atkinson D., Jin W., Sternes K., Spallone P., Stock A. D., Leppert M., Keating M. T. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993 Sep;5(1):11–16. doi: 10.1038/ng0993-11. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Finucane B. M., Jaeger E. R., Kurtz M. B., Weinstein M., Scott C. I., Jr Eye abnormalities in the Smith-Magenis contiguous gene deletion syndrome. Am J Med Genet. 1993 Feb 15;45(4):443–446. doi: 10.1002/ajmg.1320450409. [DOI] [PubMed] [Google Scholar]
  14. Fischer H., Oswald H. P., Duba H. C., Doczy L., Simma B., Utermann G., Haas O. A. Constitutional interstitial deletion of 17(p11.2) (Smith-Magenis syndrome): a clinically recognizable microdeletion syndrome. Report of two cases and review of the literature. Klin Padiatr. 1993 May-Jun;205(3):162–166. [PubMed] [Google Scholar]
  15. Friederich E., Pringault E., Arpin M., Louvard D. From the structure to the function of villin, an actin-binding protein of the brush border. Bioessays. 1990 Sep;12(9):403–408. doi: 10.1002/bies.950120902. [DOI] [PubMed] [Google Scholar]
  16. Greenberg F., Guzzetta V., Montes de Oca-Luna R., Magenis R. E., Smith A. C., Richter S. F., Kondo I., Dobyns W. B., Patel P. I., Lupski J. R. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Am J Hum Genet. 1991 Dec;49(6):1207–1218. [PMC free article] [PubMed] [Google Scholar]
  17. Guzzetta V., Franco B., Trask B. J., Zhang H., Saucedo-Cardenas O., Montes de Oca-Luna R., Greenberg F., Chinault A. C., Lupski J. R., Patel P. I. Somatic cell hybrids, sequence-tagged sites, simple repeat polymorphisms, and yeast artificial chromosomes for physical and genetic mapping of proximal 17p. Genomics. 1992 Jul;13(3):551–559. doi: 10.1016/0888-7543(92)90124-b. [DOI] [PubMed] [Google Scholar]
  18. Guzzetta V., Montes de Oca-Luna R., Lupski J. R., Patel P. I. Isolation of region-specific and polymorphic markers from chromosome 17 by restricted Alu polymerase chain reaction. Genomics. 1991 Jan;9(1):31–36. doi: 10.1016/0888-7543(91)90217-3. [DOI] [PubMed] [Google Scholar]
  19. Hedbom E., Heinegård D. Binding of fibromodulin and decorin to separate sites on fibrillar collagens. J Biol Chem. 1993 Dec 25;268(36):27307–27312. [PubMed] [Google Scholar]
  20. Kondo I., Matsuura S., Kuwajima K., Tokashiki M., Izumikawa Y., Naritomi K., Niikawa N., Kajii T. Diagnostic hand anomalies in Smith-Magenis syndrome: four new patients with del (17)(p11.2p11.2) Am J Med Genet. 1991 Nov 1;41(2):225–229. doi: 10.1002/ajmg.1320410219. [DOI] [PubMed] [Google Scholar]
  21. Kwiatkowski D. J., Stossel T. P., Orkin S. H., Mole J. E., Colten H. R., Yin H. L. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature. 1986 Oct 2;323(6087):455–458. doi: 10.1038/323455a0. [DOI] [PubMed] [Google Scholar]
  22. Le Guern E., Sturtz F., Gugenheim M., Gouider R., Bonnebouche C., Ravisé N., Gonnaud P. M., Tardieu S., Bouche P., Chazot G. Detection of deletion within 17p11.2 in 7 French families with hereditary neuropathy with liability to pressure palsies (HNPP). Cytogenet Cell Genet. 1994;65(4):261–264. doi: 10.1159/000133643. [DOI] [PubMed] [Google Scholar]
  23. Ledbetter D. H., Ledbetter S. A., vanTuinen P., Summers K. M., Robinson T. J., Nakamura Y., Wolff R., White R., Barker D. F., Wallace M. R. Molecular dissection of a contiguous gene syndrome: frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5136–5140. doi: 10.1073/pnas.86.13.5136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lee S. T., Nicholls R. D., Bundey S., Laxova R., Musarella M., Spritz R. A. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N Engl J Med. 1994 Feb 24;330(8):529–534. doi: 10.1056/NEJM199402243300803. [DOI] [PubMed] [Google Scholar]
  25. Lockwood D., Hecht F., Dowman C., Hecht B. K., Rizkallah T. H., Goodwin T. M., Allanson J. Chromosome subband 17p11.2 deletion: a minute deletion syndrome. J Med Genet. 1988 Nov;25(11):732–737. doi: 10.1136/jmg.25.11.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lupski J. R., Chance P. F., Garcia C. A. Inherited primary peripheral neuropathies. Molecular genetics and clinical implications of CMT1A and HNPP. JAMA. 1993 Nov 17;270(19):2326–2330. doi: 10.1001/jama.270.19.2326. [DOI] [PubMed] [Google Scholar]
  27. Lupski J. R., de Oca-Luna R. M., Slaugenhaupt S., Pentao L., Guzzetta V., Trask B. J., Saucedo-Cardenas O., Barker D. F., Killian J. M., Garcia C. A. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991 Jul 26;66(2):219–232. doi: 10.1016/0092-8674(91)90613-4. [DOI] [PubMed] [Google Scholar]
  28. Maumenee I. H. Vitreoretinal degeneration as a sign of generalized connective tissue diseases. Am J Ophthalmol. 1979 Sep;88(3 Pt 1):432–449. doi: 10.1016/0002-9394(79)90645-7. [DOI] [PubMed] [Google Scholar]
  29. Maury C. P., Rossi H. Demonstration of a circulating 65K gelsolin variant specific for familial amyloidosis, Finnish type. Biochem Biophys Res Commun. 1993 Feb 26;191(1):41–44. doi: 10.1006/bbrc.1993.1181. [DOI] [PubMed] [Google Scholar]
  30. Miklos G. L., De Couet H. G. The mutations previously designated as flightless-I3, flightless-O2 and standby are members of the W-2 lethal complementation group at the base of the X-chromosome of Drosophila melanogaster. J Neurogenet. 1990 Apr;6(3):133–151. doi: 10.3109/01677069009107106. [DOI] [PubMed] [Google Scholar]
  31. Patel P. I., Lupski J. R. Charcot-Marie-Tooth disease: a new paradigm for the mechanism of inherited disease. Trends Genet. 1994 Apr;10(4):128–133. doi: 10.1016/0168-9525(94)90214-3. [DOI] [PubMed] [Google Scholar]
  32. Pentao L., Wise C. A., Chinault A. C., Patel P. I., Lupski J. R. Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nat Genet. 1992 Dec;2(4):292–300. doi: 10.1038/ng1292-292. [DOI] [PubMed] [Google Scholar]
  33. Perrimon N., Smouse D., Miklos G. L. Developmental genetics of loci at the base of the X chromosome of Drosophila melanogaster. Genetics. 1989 Feb;121(2):313–331. doi: 10.1093/genetics/121.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Raeymaekers P., Timmerman V., Nelis E., De Jonghe P., Hoogendijk J. E., Baas F., Barker D. F., Martin J. J., De Visser M., Bolhuis P. A. Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group. Neuromuscul Disord. 1991;1(2):93–97. doi: 10.1016/0960-8966(91)90055-w. [DOI] [PubMed] [Google Scholar]
  35. Reiner O., Carrozzo R., Shen Y., Wehnert M., Faustinella F., Dobyns W. B., Caskey C. T., Ledbetter D. H. Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature. 1993 Aug 19;364(6439):717–721. doi: 10.1038/364717a0. [DOI] [PubMed] [Google Scholar]
  36. Roa B. B., Garcia C. A., Pentao L., Killian J. M., Trask B. J., Suter U., Snipes G. J., Ortiz-Lopez R., Shooter E. M., Patel P. I. Evidence for a recessive PMP22 point mutation in Charcot-Marie-Tooth disease type 1A. Nat Genet. 1993 Oct;5(2):189–194. doi: 10.1038/ng1093-189. [DOI] [PubMed] [Google Scholar]
  37. Shaffer L. G., McCaskill C., Han J. Y., Choo K. H., Cutillo D. M., Donnenfeld A. E., Weiss L., Van Dyke D. L. Molecular characterization of de novo secondary trisomy 13. Am J Hum Genet. 1994 Nov;55(5):968–974. [PMC free article] [PubMed] [Google Scholar]
  38. Smith A. C., McGavran L., Robinson J., Waldstein G., Macfarlane J., Zonona J., Reiss J., Lahr M., Allen L., Magenis E. Interstitial deletion of (17)(p11.2p11.2) in nine patients. Am J Med Genet. 1986 Jul;24(3):393–414. doi: 10.1002/ajmg.1320240303. [DOI] [PubMed] [Google Scholar]
  39. Stratton R. F., Dobyns W. B., Greenberg F., DeSana J. B., Moore C., Fidone G., Runge G. H., Feldman P., Sekhon G. S., Pauli R. M. Interstitial deletion of (17)(p11.2p11.2): report of six additional patients with a new chromosome deletion syndrome. Am J Med Genet. 1986 Jul;24(3):421–432. doi: 10.1002/ajmg.1320240305. [DOI] [PubMed] [Google Scholar]
  40. Sunada Y., Nakase H., Shimizu T., Mannen T., Kanazawa I. [Gene analysis of Japanese patients with familial amyloidotic polyneuropathy type IV]. Rinsho Shinkeigaku. 1992 Aug;32(8):840–844. [PubMed] [Google Scholar]
  41. Sunada Y., Shimizu T., Nakase H., Ohta S., Asaoka T., Amano S., Sawa M., Kagawa Y., Kanazawa I., Mannen T. Inherited amyloid polyneuropathy type IV (gelsolin variant) in a Japanese family. Ann Neurol. 1993 Jan;33(1):57–62. doi: 10.1002/ana.410330110. [DOI] [PubMed] [Google Scholar]
  42. Wise C. A., Garcia C. A., Davis S. N., Heju Z., Pentao L., Patel P. I., Lupski J. R. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMTIA duplication. Am J Hum Genet. 1993 Oct;53(4):853–863. [PMC free article] [PubMed] [Google Scholar]
  43. Zori R. T., Lupski J. R., Heju Z., Greenberg F., Killian J. M., Gray B. A., Driscoll D. J., Patel P. I., Zackowski J. L. Clinical, cytogenetic, and molecular evidence for an infant with Smith-Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion. Am J Med Genet. 1993 Sep 15;47(4):504–511. doi: 10.1002/ajmg.1320470414. [DOI] [PubMed] [Google Scholar]
  44. van Tuinen P., Rich D. C., Summers K. M., Ledbetter D. H. Regional mapping panel for human chromosome 17: application to neurofibromatosis type 1. Genomics. 1987 Dec;1(4):374–381. doi: 10.1016/0888-7543(87)90042-5. [DOI] [PubMed] [Google Scholar]