Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1998 Dec;35(12):1026–1030. doi: 10.1136/jmg.35.12.1026

A family with mental retardation, variable macrocephaly and macro-orchidism, and linkage to Xq12-q21.

J P Johnson 1, R Nelson 1, C E Schwartz 1
PMCID: PMC1051516  PMID: 9863601

Abstract

A family with X linked inheritance of mental retardation (XLMR) is presented. There are 10 mentally retarded males and two affected females in two generations. There are four obligatory carriers, one of whom is described as "slow". Most affected males show macrocephaly and macro-orchidism, which are typical signs of the fragile X syndrome, but have been tested cytogenetically and by analysis of the FMR1 gene and do not have this syndrome. However, some normal males in the family also exhibit macro-orchidism and macrocephaly. Linkage analysis using markers derived from the X chromosome indicates that the causative gene in this family is located in the proximal long arm of the X chromosome, in the interval Xp11-q21. Maximum lod scores of 2.96 with no recombination were found at three loci in Xq13-q21: DXS1111, DXS566, and DXS986. Recombination was observed with DXS1002 (Xq21.31) and DXS991 (Xp11.2), loci separated by about 30 Mb. Although isolation of the gene in this family will be difficult because of the size of the region involved, the localisation should be helpful in investigating other similar families with XLMR, macrocephaly, and macro-orchidism not attributable to FMR1.

Full text

PDF
1028

Images in this article

1028Image
on p.1028

Selected References

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

  1. Chiurazzi P., de Graaff E., Ng J., Verkerk A. J., Wolfson S., Fisch G. S., Kozak L., Neri G., Oostra B. A. No apparent involvement of the FMR1 gene in five patients with phenotypic manifestations of the fragile X syndrome. Am J Med Genet. 1994 Jul 15;51(4):309–314. doi: 10.1002/ajmg.1320510405. [DOI] [PubMed] [Google Scholar]
  2. Fishburn J., Turner G., Daniel A., Brookwell R. The diagnosis and frequency of X-linked conditions in a cohort of moderately retarded males with affected brothers. Am J Med Genet. 1983 Apr;14(4):713–724. doi: 10.1002/ajmg.1320140413. [DOI] [PubMed] [Google Scholar]
  3. Gedeon A. K., Donnelly A. J., Mulley J. C., Kerr B., Turner G. How many X-linked genes for non-specific mental retardation (MRX) are there? Am J Med Genet. 1996 Jul 12;64(1):158–162. doi: 10.1002/(SICI)1096-8628(19960712)64:1<158::AID-AJMG26>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  4. Gedeon A., Mulley J., Haan E. Gene localisation for Sutherland-Haan syndrome (SHS:MIM 309470) Am J Med Genet. 1996 Jul 12;64(1):78–79. doi: 10.1002/(SICI)1096-8628(19960712)64:1<78::AID-AJMG12>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  5. Gedeon A., Mulley J., Turner G. Gene localisation for Wilson-Turner syndrome (WTS:MIM 309585) Am J Med Genet. 1996 Jul 12;64(1):80–81. doi: 10.1002/(SICI)1096-8628(19960712)64:1<80::AID-AJMG13>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  6. Gibbons R. J., Picketts D. J., Villard L., Higgs D. R. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell. 1995 Mar 24;80(6):837–845. doi: 10.1016/0092-8674(95)90287-2. [DOI] [PubMed] [Google Scholar]
  7. Goldblatt J., Ballo R., Sachs B., Moosa A. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype. Clin Genet. 1989 Feb;35(2):116–120. doi: 10.1111/j.1399-0004.1989.tb02915.x. [DOI] [PubMed] [Google Scholar]
  8. Herbst D. S. Nonspecific X-linked mental retardation I: a review with information from 24 new families. Am J Med Genet. 1980;7(4):443–460. doi: 10.1002/ajmg.1320070406. [DOI] [PubMed] [Google Scholar]
  9. Horn N., Stene J., Møllekaer A. M., Friedrich U. Linkage studies in Menkes' disease. The Xg blood group system and C-banding of the X chromosome. Ann Hum Genet. 1984 May;48(Pt 2):161–172. doi: 10.1111/j.1469-1809.1984.tb01011.x. [DOI] [PubMed] [Google Scholar]
  10. Howard-Peebles P. N., Finley W. H. Screening of mentally retarded males for macro-orchidism and the fragile X chromosome. Am J Med Genet. 1983 Aug;15(4):631–635. doi: 10.1002/ajmg.1320150414. [DOI] [PubMed] [Google Scholar]
  11. Hu L. J., Blumenfeld-Heyberger S., Hanauer A., Weissenbach J., Mandel J. L. Non-specific X-linked mental retardation: linkage analysis in MRX2 and MRX4 families revisited. Am J Med Genet. 1994 Jul 15;51(4):569–574. doi: 10.1002/ajmg.1320510455. [DOI] [PubMed] [Google Scholar]
  12. Häne B., Schroer R. J., Arena J. F., Lubs H. A., Schwartz C. E., Stevenson R. E. Nonsyndromic X-linked mental retardation: review and mapping of MRX29 to Xp21. Clin Genet. 1996 Oct;50(4):176–183. doi: 10.1111/j.1399-0004.1996.tb02622.x. [DOI] [PubMed] [Google Scholar]
  13. Jennings M., Hall J. G., Hoehn H. Significance of phenotypic and chromosomal abnormalities in X-linked mental retardation (Martin-Bell or Renpenning syndrome). Am J Med Genet. 1980;7(4):417–432. doi: 10.1002/ajmg.1320070404. [DOI] [PubMed] [Google Scholar]
  14. Lubs H. A., Chiurazzi P., Arena J. F., Schwartz C., Tranebjaerg L., Neri G. XLMR genes: update 1996. Am J Med Genet. 1996 Jul 12;64(1):147–157. doi: 10.1002/(SICI)1096-8628(19960712)64:1<147::AID-AJMG25>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
  15. Nielsen K. B., Tommerup N., Dyggve H. V., Schou C. Macroorchidism and fragile X in mentally retarded males. Clinical, cytogenetic, and some hormonal investigations in mentally retarded males, including two with the fragile site at Xq28, fra(X)(q28). Hum Genet. 1982;61(2):113–117. doi: 10.1007/BF00274199. [DOI] [PubMed] [Google Scholar]
  16. Opitz J. M., Sutherland G. R. Conference report: International Workshop on the fragile X and X-linked mental retardation. Am J Med Genet. 1984 Jan;17(1):5–94. doi: 10.1002/ajmg.1320170103. [DOI] [PubMed] [Google Scholar]
  17. Schwartz C. E., Ulmer J., Brown A., Pancoast I., Goodman H. O., Stevenson R. E. Allan-Herndon syndrome. II. Linkage to DNA markers in Xq21. Am J Hum Genet. 1990 Sep;47(3):454–458. [PMC free article] [PubMed] [Google Scholar]
  18. Sugie H., Sugie Y., Nishida M., Ito M., Tsurui S., Suzuki M., Miyamoto R., Igarashi Y. Recurrent myoglobinuria in a child with mental retardation: phosphoglycerate kinase deficiency. J Child Neurol. 1989 Apr;4(2):95–99. doi: 10.1177/088307388900400203. [DOI] [PubMed] [Google Scholar]
  19. Turner G., Gedeon A., Mulley J. X-linked mental retardation with heterozygous expression and macrocephaly: pericentromeric gene localization. Am J Med Genet. 1994 Jul 15;51(4):575–580. doi: 10.1002/ajmg.1320510456. [DOI] [PubMed] [Google Scholar]
  20. Turner G., Turner B. X-linked mental retardation. J Med Genet. 1974 Jun;11(2):109–113. doi: 10.1136/jmg.11.2.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wieacker P., Wolff G., Wienker T. F. Close linkage of the Wieacker-Wolff syndrome to the DNA segment DXYS1 in proximal Xq. Am J Med Genet. 1987 Sep;28(1):245–253. doi: 10.1002/ajmg.1320280137. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES