title: A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25-q26.
abstract: X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.
authors: Academic Department of Medical Genetics and Regional Genetic Services, St Mary's Hospital, University of Manchester, Manchester, UK. deirdre.cilliers@icr.ac.uk
authors: Deirdre D
authors: DD
authors: Cilliers
authors: Rahat
authors: R
authors: Parveen
authors: Peter
authors: P
authors: Clayton
authors: Stephen A
authors: SA
authors: Cairns
authors: Sheila
authors: S
authors: Clarke
authors: Stephen M
authors: SM
authors: Shalet
authors: Graeme C M
authors: GC
authors: Black
authors: William G
authors: WG
authors: Newman
authors: Jill
authors: J
authors: Clayton-Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D019066:Facies; D005260:Female; D006130:Growth Disorders / Q000150:complications / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008831:Microcephaly / Q000150:complications / Q000235:genetics*; D018895:Microsatellite Repeats; D010375:Pedigree; D013577:Syndrome; D013733:Testicular Diseases / Q000150:complications / Q000235:genetics*