Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(24):10001–10005. doi: 10.1073/pnas.86.24.10001

Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome.

A Ballabio 1, B Bardoni 1, R Carrozzo 1, G Andria 1, D Bick 1, L Campbell 1, B Hamel 1, M A Ferguson-Smith 1, G Gimelli 1, M Fraccaro 1, et al.
PMCID: PMC298630  PMID: 2602357

Abstract

Mendelian inherited disorders due to deletions of adjacent genes on a chromosome have been described as "contiguous gene syndromes." Short stature, chondrodysplasia punctata, mental retardation, steroid sulfatase deficiency, and Kallmann syndrome have been found as isolated entities or associated in various combinations in 27 patients with interstitial and terminal deletions involving the distal short arm of the X chromosome. The use of cDNA and genomic probes from the Xp22-pter region allowed us to identify 12 different deletion intervals and to confirm, and further refine, the chromosomal assignment of X-linked recessive chondrodysplasia punctata and Kallmann syndrome genes. A putative pseudoautosomal gene affecting height and an X-linked non-specific mental retardation gene have been tentatively assigned to specific intervals. The deletion panel described is a useful tool for mapping new sequences and orienting chromosome walks in the region.

Full text

PDF
10001

Images in this article

10004Image
on p.10004

Selected References

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

  1. Affara N. A., Ferguson-Smith M. A., Magenis R. E., Tolmie J. L., Boyd E., Cooke A., Jamieson D., Kwok K., Mitchell M., Snadden L. Mapping the testis determinants by an analysis of Y-specific sequences in males with apparent XX and XO karyotypes and females with XY karyotypes. Nucleic Acids Res. 1987 Sep 25;15(18):7325–7342. doi: 10.1093/nar/15.18.7325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agematsu K., Koike K., Morosawa H., Nakahori Y., Nakagome Y., Akabane T. Chondrodysplasia punctata with X;Y translocation. Hum Genet. 1988 Sep;80(1):105–107. doi: 10.1007/BF00451470. [DOI] [PubMed] [Google Scholar]
  3. Andria G., Ballabio A., Parenti G., Di Maio S., Piccirillo A. Steroid sulphatase deficiency is present in patients with the syndrome 'ichthyosis and male hypogonadism' and with 'Rud syndrome'. J Inherit Metab Dis. 1984;7 (Suppl 2):159–160. doi: 10.1007/978-94-009-5612-4_54. [DOI] [PubMed] [Google Scholar]
  4. Arveiler B., Alembik Y., Hanauer A., Jacobs P., Tranebjaerg L., Mikkelsen M., Puissant H., Piet L. L., Mandel J. L. Linkage analysis suggests at least two loci for X-linked non-specific mental retardation. Am J Med Genet. 1988 May-Jun;30(1-2):473–483. doi: 10.1002/ajmg.1320300150. [DOI] [PubMed] [Google Scholar]
  5. Ballabio A., Carrozzo R., Gil A., Gillard B., Affara N., Ferguson-Smith M. A., Fraser N., Craig I., Rocchi M., Romeo G. Molecular characterization of human X/Y translocations suggests their aetiology through aberrant exchange between homologous sequences on Xp and Yq. Ann Hum Genet. 1989 Jan;53(Pt 1):9–14. doi: 10.1111/j.1469-1809.1989.tb01117.x. [DOI] [PubMed] [Google Scholar]
  6. Ballabio A., Carrozzo R., Parenti G., Gil A., Zollo M., Persico M. G., Gillard E., Affara N., Yates J., Ferguson-Smith M. A. Molecular heterogeneity of steroid sulfatase deficiency: a multicenter study on 57 unrelated patients, at DNA and protein levels. Genomics. 1989 Jan;4(1):36–40. doi: 10.1016/0888-7543(89)90311-x. [DOI] [PubMed] [Google Scholar]
  7. Ballabio A., Parenti G., Carrozzo R., Coppa G., Felici L., Migliori V., Silengo M., Franceschini P., Andria G. X/Y translocation in a family with X-linked ichthyosis, chondrodysplasia punctata, and mental retardation: DNA analysis reveals deletion of the steroid sulphatase gene and translocation of its Y pseudogene. Clin Genet. 1988 Jul;34(1):31–37. doi: 10.1111/j.1399-0004.1988.tb02612.x. [DOI] [PubMed] [Google Scholar]
  8. Ballabio A., Parenti G., Carrozzo R., Sebastio G., Andria G., Buckle V., Fraser N., Craig I., Rocchi M., Romeo G. Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4519–4523. doi: 10.1073/pnas.84.13.4519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ballabio A., Parenti G., Tippett P., Mondello C., Di Maio S., Tenore A., Andria G. X-linked ichthyosis, due to steroid sulphatase deficiency, associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia): linkage relationships with Xg and cloned DNA sequences from the distal short arm of the X chromosome. Hum Genet. 1986 Mar;72(3):237–240. doi: 10.1007/BF00291885. [DOI] [PubMed] [Google Scholar]
  10. Bardoni B., Guioli S., Raimondi E., Heilig R., Mandel J. L., Ottolenghi S., Camerino G. Isolation and characterization of a family of sequences dispersed on the human X chromosome. Genomics. 1988 Jul;3(1):32–38. doi: 10.1016/0888-7543(88)90155-3. [DOI] [PubMed] [Google Scholar]
  11. Bick D., Curry C. J., McGill J. R., Schorderet D. F., Bux R. C., Moore C. M. Male infant with ichthyosis, Kallmann syndrome, chondrodysplasia punctata, and an Xp chromosome deletion. Am J Med Genet. 1989 May;33(1):100–107. doi: 10.1002/ajmg.1320330114. [DOI] [PubMed] [Google Scholar]
  12. Bickmore W. A., Cooke H. J. Evolution of homologous sequences on the human X and Y chromosomes, outside of the meiotic pairing segment. Nucleic Acids Res. 1987 Aug 11;15(15):6261–6271. doi: 10.1093/nar/15.15.6261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Brunjes P. C., Frazier L. L. Maturation and plasticity in the olfactory system of vertebrates. Brain Res. 1986 Mar;396(1):1–45. doi: 10.1016/s0006-8993(86)80188-3. [DOI] [PubMed] [Google Scholar]
  14. Camerino G., Grzeschik K. H., Jaye M., De La Salle H., Tolstoshev P., Lecocq J. P., Heilig R., Mandel J. L. Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proc Natl Acad Sci U S A. 1984 Jan;81(2):498–502. doi: 10.1073/pnas.81.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cooke H. J., Brown W. R., Rappold G. A. Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature. 1985 Oct 24;317(6039):687–692. doi: 10.1038/317687a0. [DOI] [PubMed] [Google Scholar]
  16. Cremers F. P., van de Pol D. J., Diergaarde P. J., Wieringa B., Nussbaum R. L., Schwartz M., Ropers H. H. Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. Genomics. 1989 Jan;4(1):41–46. doi: 10.1016/0888-7543(89)90312-1. [DOI] [PubMed] [Google Scholar]
  17. Curry C. J., Magenis R. E., Brown M., Lanman J. T., Jr, Tsai J., O'Lague P., Goodfellow P., Mohandas T., Bergner E. A., Shapiro L. J. Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome. N Engl J Med. 1984 Oct 18;311(16):1010–1015. doi: 10.1056/NEJM198410183111603. [DOI] [PubMed] [Google Scholar]
  18. Emanuel B. S. Molecular cytogenetics: toward dissection of the contiguous gene syndromes. Am J Hum Genet. 1988 Nov;43(5):575–578. [PMC free article] [PubMed] [Google Scholar]
  19. Francke U., Ochs H. D., de Martinville B., Giacalone J., Lindgren V., Distèche C., Pagon R. A., Hofker M. H., van Ommen G. J., Pearson P. L. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet. 1985 Mar;37(2):250–267. [PMC free article] [PubMed] [Google Scholar]
  20. Fraser N., Ballabio A., Zollo M., Persico G., Craig I. Identification of incomplete coding sequences for steroid sulphatase on the human Y chromosome: evidence for an ancestral pseudoautosomal gene? Development. 1987;101 (Suppl):127–132. doi: 10.1242/dev.101.Supplement.127. [DOI] [PubMed] [Google Scholar]
  21. Gillard E. F., Affara N. A., Yates J. R., Goudie D. R., Lambert J., Aitken D. A., Ferguson-Smith M. A. Deletion of a DNA sequence in eight of nine families with X-linked ichthyosis (steroid sulphatase deficiency). Nucleic Acids Res. 1987 May 26;15(10):3977–3985. doi: 10.1093/nar/15.10.3977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Goodfellow P., Banting G., Sheer D., Ropers H. H., Caine A., Ferguson-Smith M. A., Povey S., Voss R. Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome. Nature. 1983 Mar 24;302(5906):346–349. doi: 10.1038/302346a0. [DOI] [PubMed] [Google Scholar]
  23. Koenig M., Camerino G., Heilig R., Mandel J. L. A DNA fragment from the human X chromosome short arm which detects a partially homologous sequence on the Y chromosomes long arm. Nucleic Acids Res. 1984 May 25;12(10):4097–4109. doi: 10.1093/nar/12.10.4097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kunkel L. M., Monaco A. P., Middlesworth W., Ochs H. D., Latt S. A. Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4778–4782. doi: 10.1073/pnas.82.14.4778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kunkel L. M., Tantravahi U., Kurnit D. M., Eisenhard M., Bruns G. P., Latt S. A. Identification and isolation of transcribed human X chromosome DNA sequences. Nucleic Acids Res. 1983 Nov 25;11(22):7961–7979. doi: 10.1093/nar/11.22.7961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. McCabe E. R., Towbin J., Chamberlain J., Baumbach L., Witkowski J., van Ommen G. J., Koenig M., Kunkel L. M., Seltzer W. K. Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia. J Clin Invest. 1989 Jan;83(1):95–99. doi: 10.1172/JCI113890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Middlesworth W., Bertelson C., Kunkel L. M. An RFLP detecting single copy X-chromosome fragment, dic56, from Xp22-Xpter [HGM8 assignment no. DXS 143]. Nucleic Acids Res. 1985 Aug 12;13(15):5723–5723. doi: 10.1093/nar/13.15.5723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mondello C., Ropers H. H., Craig I. W., Tolley E., Goodfellow P. N. Physical mapping of genes and sequences at the end of the human X chromosome short arm. Ann Hum Genet. 1987 May;51(Pt 2):137–143. doi: 10.1111/j.1469-1809.1987.tb01055.x. [DOI] [PubMed] [Google Scholar]
  30. Page D. C., Mosher R., Simpson E. M., Fisher E. M., Mardon G., Pollack J., McGillivray B., de la Chapelle A., Brown L. G. The sex-determining region of the human Y chromosome encodes a finger protein. Cell. 1987 Dec 24;51(6):1091–1104. doi: 10.1016/0092-8674(87)90595-2. [DOI] [PubMed] [Google Scholar]
  31. Rouyer F., Simmler M. C., Johnsson C., Vergnaud G., Cooke H. J., Weissenbach J. A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes. Nature. 1986 Jan 23;319(6051):291–295. doi: 10.1038/319291a0. [DOI] [PubMed] [Google Scholar]
  32. Schmickel R. D. Contiguous gene syndromes: a component of recognizable syndromes. J Pediatr. 1986 Aug;109(2):231–241. doi: 10.1016/s0022-3476(86)80377-8. [DOI] [PubMed] [Google Scholar]
  33. Schwanzel-Fukuda M., Pfaff D. W. Origin of luteinizing hormone-releasing hormone neurons. Nature. 1989 Mar 9;338(6211):161–164. doi: 10.1038/338161a0. [DOI] [PubMed] [Google Scholar]
  34. Shapiro L. J. Steroid sulfatase deficiency and the genetics of the short arm of the human X chromosome. Adv Hum Genet. 1985;14:331-81, 388-9. doi: 10.1007/978-1-4615-9400-0_5. [DOI] [PubMed] [Google Scholar]
  35. Sunohara N., Sakuragawa N., Satoyoshi E., Tanae A., Shapiro L. J. A new syndrome of anosmia, ichthyosis, hypogonadism, and various neurological manifestations with deficiency of steroid sulfatase and arylsulfatase C. Ann Neurol. 1986 Feb;19(2):174–181. doi: 10.1002/ana.410190211. [DOI] [PubMed] [Google Scholar]
  36. Suthers G. K., Turner G., Mulley J. C. A non-syndromal form of X-linked mental retardation (XLMR) is linked to DXS14. Am J Med Genet. 1988 May-Jun;30(1-2):485–491. doi: 10.1002/ajmg.1320300151. [DOI] [PubMed] [Google Scholar]
  37. Tiepolo L., Zuffardi O., Fraccaro M., di Natale D., Gargantini L., Müller C. R., Ropers H. H. Assignment by deletion mapping of the steroid sulfatase X-linked ichthyosis locus to Xp223. Hum Genet. 1980;54(2):205–206. doi: 10.1007/BF00278973. [DOI] [PubMed] [Google Scholar]
  38. Wegenke J. D., Uehling D. T., Wear J. B., Jr, Gordon E. S., Bargman J. G., Deacon J. S., Herrmann J. P., Opitz J. M. Familial Kallmann syndrome with unilateral renal aplasia. Clin Genet. 1975 May-Jun;7(5):368–381. doi: 10.1111/j.1399-0004.1975.tb00344.x. [DOI] [PubMed] [Google Scholar]
  39. Yen P. H., Allen E., Marsh B., Mohandas T., Wang N., Taggart R. T., Shapiro L. J. Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell. 1987 May 22;49(4):443–454. doi: 10.1016/0092-8674(87)90447-8. [DOI] [PubMed] [Google Scholar]
  40. Zuffardi O., Maraschio P., Lo Curto F., Müller U., Giarola A., Perotti L. The role of Yp in sex determination: new evidence from X/Y translocations. Am J Med Genet. 1982 Jun;12(2):175–184. doi: 10.1002/ajmg.1320120207. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES