No evidence for triallelic inheritance of MKKS/BBS loci in Amish Mckusick-Kaufman syndrome.
It has been hypothesized that two mutations in one gene are not sufficient and that three mutations between two genes are required for penetrance in some cases of Bardet-Biedl syndrome (the so-called "triallelic inheritance" model). McKusick-Kaufman syndrome (MKS) is allelic to one form of Bardet-Biedl syndrome (BBS). We describe an Amish family with MKS, where three children were affected with homozygous MKKS (BBS6) mutations (H84Y and A242S on both alleles), their father was a carrier, and their mother was homozygous for the same MKKS mutations, but she was non-penetrant. Genotyping and/or sequencing of BBS1, BBS2, BBS3, BBS4, BBS5, BBS7, and BBS8 excluded "triallelic inheritance" for each gene either by an incompatible inheritance pattern or an absence of mutations in the coding region and the intronic splice junctions of these genes. We conclude that the "triallelic" model does not explain the incomplete penetrance of MKS.
Nakane
Takaya
T
Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biesecker
Leslie G
LG
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D020788:Bardet-Biedl Syndrome / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006330:Heart Defects, Congenital / Q000473:pathology; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D017689:Polydactyly / Q000473:pathology; D011506:Proteins / Q000235:genetics; D013577:Syndrome
C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins