Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation

We have recently shown that mutations in oligophrenin-1 (OPHN1) are respons ible for non-specific X-linked mental retardation (MRX). The structure of t he gene encoding the OPHN1 protein was determined by isolation of genomic D NA clones from the human cosmid library. Genomic fragments containing exons were sequenced, and the sequences of the exons and flanking introns were d efined. Knowledge of the genomic structure of the OPHN1 gene, which spans a t least 500 kb and consists of 25 exons, will Facilitate the search for add itional mutations in OPHN1. OPHN1 was screened for mutations in 164 subject s with non-specific mental retardation. Three nucleotide substitutions were identified, one of which was a silent mutation in the codon threonine 301 at position 903 (G --> C). The other substitutions were located in exon 2, a G --> A substitution at position 133 (A45T), and in exon 10, a C --> T su bstitution at position 902 (T301M), but these are common polymorphisms rath er than disease-causing mutations. (C) 2000 Editions scientifiques et medic ales Elsevier SAS.