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. 2002 Feb;39(2):105–109. doi: 10.1136/jmg.39.2.105

A locus for isolated cataract on human Xp

P Francis 1, V Berry 1, A Hardcastle 1, E Maher 1, A Moore 1, S Bhattacharya 1
PMCID: PMC1735039  PMID: 11836358

Abstract

Purpose: To genetically map the gene causing isolated X linked cataract in a large European pedigree.

Methods: Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing.

Results: The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at θ=0 for marker DXS8036).

Conclusions: This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome.

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Selected References

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  1. Aalfs C. M., Oosterwijk J. C., van Schooneveld M. J., Begeman C. J., Wabeke K. B., Hennekam R. C. Cataracts, radiculomegaly, septal heart defects and hearing loss in two unrelated adult females with normal intelligence and similar facial appearance: confirmation of a syndrome? Clin Dysmorphol. 1996 Apr;5(2):93–103. doi: 10.1097/00019605-199604000-00001. [DOI] [PubMed] [Google Scholar]
  2. Berry V., Ionides A. C., Moore A. T., Plant C., Bhattacharya S. S., Shiels A. A locus for autosomal dominant anterior polar cataract on chromosome 17p. Hum Mol Genet. 1996 Mar;5(3):415–419. doi: 10.1093/hmg/5.3.415. [DOI] [PubMed] [Google Scholar]
  3. Bixler D., Higgins M., Hartsfield J., Jr The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females. Clin Genet. 1984 Jul;26(1):30–35. doi: 10.1111/j.1399-0004.1984.tb00783.x. [DOI] [PubMed] [Google Scholar]
  4. Cassidy L., Taylor D. Congenital cataract and multisystem disorders. Eye (Lond) 1999 Jun;13(Pt 3B):464–473. doi: 10.1038/eye.1999.123. [DOI] [PubMed] [Google Scholar]
  5. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  6. Foster A., Gilbert C. Epidemiology of childhood blindness. Eye (Lond) 1992;6(Pt 2):173–176. doi: 10.1038/eye.1992.34. [DOI] [PubMed] [Google Scholar]
  7. Frances R., Rodriguez Benitez A. M., Cohen D. R. Arrhythmogenic right ventricular dysplasia and anterior polar cataract. Am J Med Genet. 1997 Dec 12;73(2):125–126. doi: 10.1002/(sici)1096-8628(19971212)73:2<125::aid-ajmg4>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  8. Francis P. J., Berry V., Moore A. T., Bhattacharya S. Lens biology: development and human cataractogenesis. Trends Genet. 1999 May;15(5):191–196. doi: 10.1016/s0168-9525(99)01738-2. [DOI] [PubMed] [Google Scholar]
  9. Franco E., Hodgson S., Lench N., Roberts G. J. Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis. Oral Dis. 1995 Mar;1(1):8–11. doi: 10.1111/j.1601-0825.1995.tb00150.x. [DOI] [PubMed] [Google Scholar]
  10. Gorlin R. J., Marashi A. H., Obwegeser H. L. Oculo-facio-cardio-dental (OFCD) syndrome. Am J Med Genet. 1996 May 3;63(1):290–292. doi: 10.1002/(SICI)1096-8628(19960503)63:1<290::AID-AJMG47>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  11. Héon E., Priston M., Schorderet D. F., Billingsley G. D., Girard P. O., Lubsen N., Munier F. L. The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999 Nov;65(5):1261–1267. doi: 10.1086/302619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ionides A., Francis P., Berry V., Mackay D., Bhattacharya S., Shiels A., Moore A. Clinical and genetic heterogeneity in autosomal dominant cataract. Br J Ophthalmol. 1999 Jul;83(7):802–808. doi: 10.1136/bjo.83.7.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jakobs P. M., Hess J. F., FitzGerald P. G., Kramer P., Weleber R. G., Litt M. Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2. Am J Hum Genet. 2000 Mar 16;66(4):1432–1436. doi: 10.1086/302872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krill A. E., Woodbury G., Bowman J. E. X-chromosomal-linked sutural cataracts. Am J Ophthalmol. 1969 Nov;68(5):867–872. doi: 10.1016/0002-9394(69)94582-6. [DOI] [PubMed] [Google Scholar]
  15. Krutovskikh V., Yamasaki H. Connexin gene mutations in human genetic diseases. Mutat Res. 2000 Apr;462(2-3):197–207. doi: 10.1016/s1383-5742(00)00037-5. [DOI] [PubMed] [Google Scholar]
  16. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lindor N. M., Michels V. V., Hoppe D. A., Driscoll D. J., Leavitt J. A., Dewald G. W. Xp22.3 microdeletion syndrome with microphthalmia, sclerocornea, linear skin defects, and congenital heart defects. Am J Med Genet. 1992 Sep 1;44(1):61–65. doi: 10.1002/ajmg.1320440115. [DOI] [PubMed] [Google Scholar]
  18. Schulze B. R., Horn D., Kobelt A., Tariverdian G., Stellzig A. Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients. Am J Med Genet. 1999 Feb 19;82(5):429–435. doi: 10.1002/(sici)1096-8628(19990219)82:5<429::aid-ajmg13>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  19. Seow W. K., Brown J. P., Romaniuk K. The Nance-Horan syndrome of dental anomalies, congenital cataracts, microphthalmia, and anteverted pinna: case report. Pediatr Dent. 1985 Dec;7(4):307–311. [PubMed] [Google Scholar]
  20. Shiels A., Mackay D., Ionides A., Berry V., Moore A., Bhattacharya S. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am J Hum Genet. 1998 Mar;62(3):526–532. doi: 10.1086/301762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stambolian D., Favor J., Silvers W., Avner P., Chapman V., Zhou E. Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome. Genomics. 1994 Jul 15;22(2):377–380. doi: 10.1006/geno.1994.1398. [DOI] [PubMed] [Google Scholar]
  22. Toutain A., Ayrault A. D., Moraine C. Mental retardation in Nance-Horan syndrome: clinical and neuropsychological assessment in four families. Am J Med Genet. 1997 Aug 22;71(3):305–314. doi: 10.1002/(sici)1096-8628(19970822)71:3<305::aid-ajmg11>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  23. Toutain A., Ronce N., Dessay B., Robb L., Francannet C., Le Merrer M., Briard M. L., Kaplan J., Moraine C. Nance-Horan syndrome: linkage analysis in 4 families refines localization in Xp22.31-p22.13 region. Hum Genet. 1997 Feb;99(2):256–261. doi: 10.1007/s004390050349. [DOI] [PubMed] [Google Scholar]
  24. Walpole S. M., Ronce N., Grayson C., Dessay B., Yates J. R., Trump D., Toutain A. Exclusion of RAI2 as the causative gene for Nance-Horan syndrome. Hum Genet. 1999 May;104(5):410–411. doi: 10.1007/s004390050976. [DOI] [PubMed] [Google Scholar]
  25. Warburg M. X-linked cataract and X-linked microphthalmos: how many deletion families? Am J Med Genet. 1989 Nov;34(3):451–453. doi: 10.1002/ajmg.1320340324. [DOI] [PubMed] [Google Scholar]
  26. Wilkie A. O., Taylor D., Scambler P. J., Baraitser M. Congenital cataract, microphthalmia and septal heart defect in two generations: a new syndrome? Clin Dysmorphol. 1993 Apr;2(2):114–119. [PubMed] [Google Scholar]

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