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J Med Genet. 1999 October; 36(10): 759–766.
PMCID: PMC1734236

X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27


To date over 150 X linked mental retardation (XLMR) conditions have been documented. We describe a five generation South African family with XLMR, comprising 16 affected males and 10 carrier females. The clinical features common to the 16 males included profound mental retardation (100%), mutism despite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limited life expectancy (68.8%). Of the four affected males examined, all had mild craniofacial dysmorphology and three were noted to have bilateral ophthalmoplegia and truncal ataxia. Three of 10 obligate female carriers had mild mental retardation. Cerebellar and brain stem atrophy was shown by cranial imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10.

Keywords: X linked mental retardation; epilepsy; cerebellar atrophy; ophthalmoplegia

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Selected References

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  • Lehrke R. Theory of X-linkage of major intellectual traits. Am J Ment Defic. 1972 May;76(6):611–619. [PubMed]
  • Sutherland GR. Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science. 1977 Jul 15;197(4300):265–266. [PubMed]
  • Neri G, Gurrieri F, Gal A, Lubs HA. XLMR genes: update 1990. Am J Med Genet. 1991 Feb-Mar;38(2-3):186–189. [PubMed]
  • Lubs HA, Chiurazzi P, Arena JF, Schwartz C, Tranebjaerg L, Neri G. XLMR genes: update 1996. Am J Med Genet. 1996 Jul 12;64(1):147–157. [PubMed]
  • Schwartz CE, Ulmer J, Brown A, Pancoast I, Goodman HO, Stevenson RE. Allan-Herndon syndrome. II. Linkage to DNA markers in Xq21. Am J Hum Genet. 1990 Sep;47(3):454–458. [PubMed]
  • Sixth International Workshop on Human X Chromosome Mapping 1995. Banff, Alberta, Canada, June 16-18, 1995. Report and abstracts. Cytogenet Cell Genet. 1995;71(4):307–342. [PubMed]
  • Lathrop GM, Lalouel JM, White RL. Construction of human linkage maps: likelihood calculations for multilocus linkage analysis. Genet Epidemiol. 1986;3(1):39–52. [PubMed]
  • Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet. 1992 Dec;51(6):1229–1239. [PubMed]
  • Pegoraro E, Schimke RN, Arahata K, Hayashi Y, Stern H, Marks H, Glasberg MR, Carroll JE, Taber JW, Wessel HB, et al. Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females. Am J Hum Genet. 1994 Jun;54(6):989–1003. [PubMed]
  • Turner G, Collins E, Turner B. Recurrence risk of mental retardation in sibs. Med J Aust. 1971 May 29;1(22):1165–1167. [PubMed]
  • Glass IA. X linked mental retardation. J Med Genet. 1991 Jun;28(6):361–371. [PMC free article] [PubMed]
  • Arena JF, Schwartz C, Stevenson R, Lawrence L, Carpenter A, Duara R, Ledbetter D, Huang T, Lehner T, Ott J, et al. Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome. Am J Med Genet. 43(1-2):479–490. [PubMed]
  • Gustavson KH, Annerén G, Malmgren H, Dahl N, Ljunggren CG, Bäckman H. New X-linked syndrome with severe mental retardation, severely impaired vision, severe hearing defect, epileptic seizures, spasticity, restricted joint mobility, and early death. Am J Med Genet. 1993 Mar 1;45(5):654–658. [PubMed]
  • Kremer H, Hamel BC, van den Helm B, Arts WF, de Wijs IJ, Sistermans EA, Ropers HH, Mariman EC. Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood. Hum Genet. 1996 Nov;98(5):513–517. [PubMed]
  • Hamel BC, Smits AP, Otten BJ, van den Helm B, Ropers HH, Mariman EC. Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings. Am J Med Genet. 1996 Jul 12;64(1):35–41. [PubMed]
  • Gedeon AK, Kozman HM, Robinson H, Pilia G, Schlessinger D, Turner G, Mulley JC. Refinement of the background genetic map of Xq26-q27 and gene localisation for Börjeson-Forssman-Lehmann Syndrome. Am J Med Genet. 1996 Jul 12;64(1):63–68. [PubMed]
  • Wijker M, Ligtenberg MJ, Schoute F, Defesche JC, Pals G, Bolhuis PA, Ropers HH, Hulsebos TJ, Menko FH, van Oost BA, et al. The gene for hereditary bullous dystrophy, X-linked macular type, maps to the Xq27.3-qter region. Am J Hum Genet. 1995 May;56(5):1096–1100. [PubMed]
  • Schimke RN, Horton WA, Collins DL, Therou L. A new X-linked syndrome comprising progressive basal ganglion dysfunction, mental and growth retardation, external ophthalmoplegia, postnatal microcephaly and deafness. Am J Med Genet. 1984 Jan;17(1):323–332. [PubMed]
  • Jolly DJ, Okayama H, Berg P, Esty AC, Filpula D, Bohlen P, Johnson GG, Shively JE, Hunkapillar T, Friedmann T. Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase. Proc Natl Acad Sci U S A. 1983 Jan;80(2):477–481. [PubMed]
  • Silver DN, Lewis RA, Nussbaum RL. Mapping the Lowe oculocerebrorenal syndrome to Xq24-q26 by use of restriction fragment length polymorphisms. J Clin Invest. 1987 Jan;79(1):282–285. [PMC free article] [PubMed]
  • Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996 Mar;12(3):241–247. [PubMed]

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