McKusick-Kaufman syndrome (MKKS, MIM 236700) is a human developmental anomaly 
syndrome comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP) and 
congenital heart disease (CHD). MKKS has been mapped in the Old Order Amish 
population to 20p12, between D20S162 and D20S894 (ref. 3). Here we describe the 
identification of a gene mutated in MKKS. We analysed the approximately 450-kb 
candidate region by sample sequencing, which revealed the presence of several 
known genes and EST clusters. We evaluated candidate transcripts by 
northern-blot analysis of adult and fetal tissues. We selected one transcript 
with widespread expression, MKKS, for analysis in a patient from the Amish 
pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found 
to be homozygous for an allele that had two missense substitutions and the 
non-Amish patient was a compound heterozygote for a frameshift mutation 
predicting premature protein truncation and a distinct missense mutation. The 
MKKS predicted protein shows amino acid similarity to the chaperonin family of 
proteins, suggesting a role for protein processing in limb, cardiac and 
reproductive system development. We believe that this is the first description 
of a human disorder caused by mutations affecting a putative chaperonin 
molecule.