ClinVar

In affected members of 2 large unrelated 5-generation Mexican kindreds segregating autosomal dominant triphalangeal thumb and/or preaxial polydactyly (PPD2; 174500), VanderMeer et al. (2014) identified heterozygosity for a c.402C-T transition in the ZRS region of the LMBR1 gene (chr7:156,584,168; GRCh37). In 1 family, a father with mild radioulnar synostosis and 3 children with isolated triphalangeal thumb were heterozygous for the mutation, which was not present in a fourth, unaffected child. In the other family, both parents of the proband had abnormal thumbs and were heterozygous for the mutation, whereas the proband, who had a more severe phenotype involving tibial and radioulnar hypoplasia, preaxial polydactyly of the hands and feet, and short triphalangeal thumbs (THYP; 188740), was homozygous for the mutation, suggestive of a dosage effect. Functional analysis using a transgenic mouse enhancer assay demonstrated ectopic expression into the anterior limb bud with the mutant.