Medknow Publications on behalf of Indian Society of Human Genetics
Abstract
McKusick-Kaufman syndrome (MKS, OMIM #236700) is a rare syndrome
inherited in an autosomal recessive pattern with a phenotypic triad
comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP), and
congenital cardiac disease (CHD). The syndrome is caused by mutations
in the MKKS gene mapped onto chromosome 20p12 between D20S162 and
D20S894 markers. Mutations in the same gene causes Bardet-Biedl-6
syndrome (BBS-6, OMIM #209900) inherited in an autosomal recessive
pattern. BBS-6 comprises retinitis pigmentosa, polydactyly, obesity,
mental retardation, renal and genital anomalies. HMC, CHD, and PAP
defects can also occur in BBS-6, and there is a significant clinical
overlap between MKS and BBS-6 in childhood. We describe a new
borderline case of MKS and BBS syndrome and suggest insights for
understanding correlation between MKKS gene mutations and clinical
phenotype. Here, we report the results of molecular analysis of MKKS in
a female proband born in an Italian nonconsanguineous healthy family
that presents HMC and PAP. The mutational screening revealed the
presence of two different heterozygous missense variants (p.242A>S
in exon 3, p.339 I>V in exon 4) in the MKKS gene, and a nucleotide
variation in 5\u2032UTR region in exon 2 (-417 A>C)