McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and 
congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising 
retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and 
genital anomalies. Bardet-Biedl syndrome is genetically heterogeneous with three 
cloned genes ( BBS2, BBS4, and MKKS) and at least three other known loci ( BBS1, 
BBS3, and BBS5). Both McKusick-Kaufman syndrome and Bardet-Biedl syndrome are 
inherited in an autosomal recessive pattern, and both syndromes are caused by 
mutations in the MKKS gene. However, mutations in MKKS are found in only 4%-11% 
of unselected Bardet-Biedl syndrome patients. We hypothesized that an analysis 
of patients with atypical Bardet-Biedl syndrome and McKusick-Kaufman syndrome 
(Group I; 15 probands) and patients with Bardet-Biedl syndrome who had linkage 
results inconsistent with linkage to the other loci (Group II; 12 probands) 
could increase the MKKS mutation yield. Both mutant alleles were identified in 
only two families in Group II. Single (heterozygous) sequence variations were 
found in three Group I families and in two Group II families. Combining these 
results with previously published data showed that only one mutant allele was 
detected in nearly half of all patients screened to date, suggesting that 
unusual mutational mechanisms or patterns of inheritance may be involved. 
However, sequencing of the BBS2 gene in these patients did not provide any 
evidence of digenic or "triallelic" inheritance. The frequency of detected 
mutations in MKKS in Group II patients was 24%, i.e., six times higher than the 
published rate for unselected BBS patients, suggesting that small-scale linkage 
analyses may be useful in suitable families.