Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2)

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recess ive disorder with the primary clinical features of obesity, pigmented retin opathy, polydactyly, hypogenitalism, mental retardation and renal anomalies . Associated features of the disorder include diabetes mellitus, hypertensi on and congenital heart disease. There are six known BBS loci, mapping to c hromosomes 2, 3, 11, 15, 15 and 20. The BBS2 locus was initially mapped to an 18 cM interval on chromosome 16q21 with a large inbred Bedouin kindred. Further analysis of the Bedouin population allowed for the fine mapping of this locus to a 2 cM region distal to marker D16S408. Physical mapping and sequence analysis of this region resulted in the identification of a number of known genes and expressed sequence tag clusters. Mutation screening of a novel gene (BBS2) with a wide pattern of tissue expression revealed homoz ygous mutations in two inbred pedigrees, including the large Bedouin kindre d used to initially identify the BBS2 locus. In addition, mutations were fo und in three of 18 unrelated BBS probands from small nuclear families.