Bardet‐Biedl syndrome type 3 in an Iranian family: Clinical study and confirmation of disease localization

Bardet‐Biedl syndrome (BBS) is a group of autosomal recessive MCA/MR syndromes characterized by pigmentary retinopathy, postaxial polydactyly, hypogenitalism, obesity, and mental retardation. Five BBS loci have been identified; among them, BBS type 1 (BBS1) and type 3 (BBS3) are most common and most rare, respectively. We encountered an Iranian family that had seven affected members. All patients had a history of mild to severe obesity, but it was reversible in some patients by caloric restriction and exercise. All patients had pigmentary retinopathy, beginning as night blindness in early childhood and progressing toward severe impairment of vision by the end of the second decade. Polydactyly varied in limb distribution, ranging from four‐limb involvement to random involvement or even to nonaffectedness. Six of the seven patients were not mentally retarded. Although kidney anomaly or an adrenal mass was pres‐ ent in two patients, the fact that one patient had seven children rules out reproductive dysfunction. Linkage analysis with microsatellite markers showed that the disease in the family was assigned to a region around marker loci at 3p13‐p12 (maximum LOD score = 4.15 and recombination fraction θ = 0, at D3S1603 microsatellite marker), to which the BBS3 locus has been mapped. Haplotype analysis did not reduce the extent of the previously reported critical region of BBS3. A comparison of clinical manifestations of our patients with those of previously reported BBS3 patients did not support any type‐specific phenotypes, though manifestations in our patients are similar to those in BBS3 patients of a family in Newfoundland. Am. J. Med. Genet. 94:433–437, 2000. © 2000 Wiley‐Liss, Inc.