Evaluation and molecular characterization of EHD1, a candidate gene for Bardet-Biedl Syndrome 1 (BBS1)

Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterize d by developmental abnormalities including mental retardation, obesity, ret initis pigmentosa, polydactyly, short stature, and hypogenitalism. To date, five BBS loci have been identified. BBS1, located on 11q13, is reported to be the most prevalent form of BBS in the Caucasian population. A positiona l cloning approach is being used to identify the gene responsible for BBS1. EHD1, a new member of the EH-domain containing proteins, was identified in this study as lying within the BBS1 disease interval. RNA analysis of many tissues revealed that expression of EHD1 is ubiquitous, with elevated leve ls in the testis. The genomic structure of EHD1 was elucidated by direct BA C sequencing. Following identification of the intron/exon boundaries, mutat ional analysis was performed by single strand conformation polymorphism and direct sequencing of affected individuals from several large kindreds link ed to the BBS1 locus, as well as a cohort of unrelated probands. No disease -causing mutations were identified in this analysis, but several polymorphi sms were found. (C) 1999 Elsevier Science B.V. All rights reserved.