title: Report of two brothers with short stature, microcephaly, mental retardation, and retinoschisis-A new mental retardation syndrome?
abstract: Involvement of genes on the X-chromosome as a cause of mental retardation has been recognized for a long time. X-linked phenotypes of mental retardation have been divided into non-syndromic and syndromic based on associated manifestations. At present, more than 140 syndromic X-linked mental retardation (XLMR) conditions have been reported and a causative gene mutation has been identified in almost half of these. Here, we report on two brothers with short stature, microcephaly, severe mental retardation, and retinoschisis. Results of karyotype analysis, fragile-X and neuroimaging studies were normal. Fundus examination showed bilateral retinoschisis at variable stages in both sibs. X-linked retinoschisis is a retinal dystrophy caused by mutations in the RS1 gene at Xp22.1, which lead to splitting of the neural retina and reduced visual acuity in affected men. However, as yet there have been no reports of mental retardation in X-linked retinoschisis although genetic loci for XLMR and short stature have been mapped to Xp22.1. Sequencing and microarray analysis failed to find any alteration of RS1 gene or copy number alteration in the region. In addition, genotype analysis of Xp22.1 provided evidence against linkage to this region. The associated findings of retinoschisis and mental retardation in two brothers suggest a new mental retardation syndrome likely to be an X linked trait.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. shubha@sgpgi.ac.in
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
authors.forename: Sheetal
authors.initials: S
authors.lastname: Sharda
authors.forename: Jill
authors.initials: J
authors.lastname: Urquhart
authors.forename: Emma
authors.initials: E
authors.lastname: Jenkinson
authors.forename: Shobhit
authors.initials: S
authors.lastname: Chawala
authors.forename: Dorothy
authors.initials: D
authors.lastname: Trump
mesh_terms: D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004392:Dwarfism / Q000235:genetics / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology*; D007621:Karyotyping; D008297:Male; D046228:Microarray Analysis; D008831:Microcephaly / Q000235:genetics / Q000473:pathology*; D041441:Retinoschisis / Q000235:genetics / Q000473:pathology*; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D005136:Eye Proteins; C108726:RS1 protein, human