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. 1997 Feb;34(2):158–160. doi: 10.1136/jmg.34.2.158

Androgen insensitivity with mental retardation: a contiguous gene syndrome?

H R Davies 1, I A Hughes 1, M O Savage 1, C A Quigley 1, M Trifiro 1, L Pinsky 1, T R Brown 1, M N Patterson 1
PMCID: PMC1050872  PMID: 9039995

Abstract

We present data to suggest the existence of a mental retardation (MR) locus at Xq11.2-q12 between DXS1 and DXS905, identified in two subjects with complete androgen insensitivity syndrome (CAIS) and MR. Androgen insensitivity syndrome is a disorder of male sexual differentiation caused by a defect in the androgen receptor (AR) gene (Xq11-q12). Two subjects with CAIS resulting from a complete deletion of the AR gene have previously been reported, one of whom also has MR. We have identified another mentally retarded person with a complete deletion of the AR gene. The deletion in the two patients with CAIS and MR extends past the AR gene and includes several marker loci both proximal and distal to the AR gene, the limits of the deletions being DXS1 and DXS905. The deletions in the CAIS patients who do not have MR do not include any of the markers outside the AR gene itself. These data suggest that located close to the AR gene is a gene which is implicated in non-specific MR.

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Selected References

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  1. Barker D. F., Fain P. R. Definition and mapping of STSs at STR and RFLP loci in Xp11-Xq22. Genomics. 1993 Dec;18(3):712–716. doi: 10.1016/s0888-7543(05)80381-7. [DOI] [PubMed] [Google Scholar]
  2. Batch J. A., Williams D. M., Davies H. R., Brown B. D., Evans B. A., Hughes I. A., Patterson M. N. Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome. Hum Mol Genet. 1992 Oct;1(7):497–503. doi: 10.1093/hmg/1.7.497. [DOI] [PubMed] [Google Scholar]
  3. Brown T. R., Lubahn D. B., Wilson E. M., Joseph D. R., French F. S., Migeon C. J. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity in this syndrome. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8151–8155. doi: 10.1073/pnas.85.21.8151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Browne D. L., Zonana J., Litt M. Dinucleotide repeat polymorphism at the PGK1P1 locus. Nucleic Acids Res. 1992 Mar 11;20(5):1169–1169. doi: 10.1093/nar/20.5.1169-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cole C. G., Goodfellow P. N., Bobrow M., Bentley D. R. Generation of novel sequence tagged sites (STSs) from discrete chromosomal regions using Alu-PCR. Genomics. 1991 Jul;10(3):816–826. doi: 10.1016/0888-7543(91)90468-t. [DOI] [PubMed] [Google Scholar]
  6. Fletcher F. A., Carpenter M. K., Shilling H., Baum P., Ziegler S. F., Gimpel S., Hollingsworth T., Vanden Bos T., James L., Hjerrild K. LERK-2, a binding protein for the receptor-tyrosine kinase ELK, is evolutionarily conserved and expressed in a developmentally regulated pattern. Oncogene. 1994 Nov;9(11):3241–3247. [PubMed] [Google Scholar]
  7. Fletcher F. A., Huebner K., Shaffer L. G., Fairweather N. D., Monaco A. P., Müller U., Druck T., Simoneaux D. K., Chelly J., Belmont J. W. Assignment of the gene (EPLG2) encoding a high-affinity binding protein for the receptor tyrosine kinase elk to a 200-kilobasepair region in human chromosome Xq12. Genomics. 1995 Jan 1;25(1):334–335. doi: 10.1016/0888-7543(95)80156-g. [DOI] [PubMed] [Google Scholar]
  8. Gottlieb B., Trifiro M., Lumbroso R., Vasiliou D. M., Pinsky L. The androgen receptor gene mutations database. Nucleic Acids Res. 1996 Jan 1;24(1):151–154. doi: 10.1093/nar/24.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hiort O., Sinnecker G. H., Holterhus P. M., Nitsche E. M., Kruse K. The clinical and molecular spectrum of androgen insensitivity syndromes. Am J Med Genet. 1996 May 3;63(1):218–222. doi: 10.1002/(SICI)1096-8628(19960503)63:1<218::AID-AJMG38>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  10. Kere J., Grzeschik K. H., Limon J., Gremaud M., Schlessinger D., de la Chapelle A. Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes. Genomics. 1993 May;16(2):305–310. doi: 10.1006/geno.1993.1189. [DOI] [PubMed] [Google Scholar]
  11. Lhoták V., Greer P., Letwin K., Pawson T. Characterization of elk, a brain-specific receptor tyrosine kinase. Mol Cell Biol. 1991 May;11(5):2496–2502. doi: 10.1128/mcb.11.5.2496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Mahtani M. M., Willard H. F. A polymorphic X-linked tetranucleotide repeat locus displaying a high rate of new mutation: implications for mechanisms of mutation at short tandem repeat loci. Hum Mol Genet. 1993 Apr;2(4):431–437. doi: 10.1093/hmg/2.4.431. [DOI] [PubMed] [Google Scholar]
  14. Patterson M. N., Hughes I. A., Gottlieb B., Pinsky L. The androgen receptor gene mutations database. Nucleic Acids Res. 1994 Sep;22(17):3560–3562. [PMC free article] [PubMed] [Google Scholar]
  15. Quigley C. A., Friedman K. J., Johnson A., Lafreniere R. G., Silverman L. M., Lubahn D. B., Brown T. R., Wilson E. M., Willard H. F., French F. S. Complete deletion of the androgen receptor gene: definition of the null phenotype of the androgen insensitivity syndrome and determination of carrier status. J Clin Endocrinol Metab. 1992 Apr;74(4):927–933. doi: 10.1210/jcem.74.4.1347772. [DOI] [PubMed] [Google Scholar]
  16. 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. doi: 10.1159/000134135. [DOI] [PubMed] [Google Scholar]
  17. Trifiro M., Gottlieb B., Pinsky L., Kaufman M., Prior L., Belsham D. D., Wrogemann K., Brown C. J., Willard H. F., Trapman J. The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene. Mol Cell Endocrinol. 1991 Jan;75(1):37–47. doi: 10.1016/0303-7207(91)90243-l. [DOI] [PubMed] [Google Scholar]

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