EXCLUSION OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR (GRPR) LOCUS AS ACANDIDATE GENE FOR RETT-SYNDROME

The gene for the gastrin-releasing peptide receptor (GRPR) has been ma pped to a candidate region for Rett syndrome (RTT) on the short arm of the X chromosome. The recent report of a translocation that disrupted the gene in an individual with mental retardation and autistic behavi or prompted us to examine GRPR as a possible locus for RTT, Genomic po lymerase chain reaction amplification of exons followed by single-stra nd conformation analysis screening in 25 unrelated RTT-affected indivi duals and by direct sequencing in 12 others has failed to detect any m utation. No gross structural rearrangements were found by Southern ana lysis of DNA from six unrelated RTT-affected individuals. A high-frequ ency biallelic polymorphism caused by two single nucleotide substituti ons in exon 2 was discovered. The allele frequencies were identical in the RTT population as compared to 100 normal control X chromosomes. T his polymorphism will enable future evaluation of the GRPR locus as a candidate for other X-linked mental retardation or neurobehavioral syn dromes. Am. J, Med. Genet. 78:173-175, 1998. (C) 1998 Wiley-Liss, Inc.