Multiple SLC26A2 mutations occurring in a three-generational family

Multiple epiphyseal dysplasias (MED) are a group of heterogeneous skeletal dysplasias, which share a common phenotype: short stature, skeletal deformities, joint pain and early onset osteoarthritis. Mutations in COMP account for approximately half of autosomal dominant MED cases whilst SLC26A2 mutations account for ∼25% of the recessive cases in the Caucasian population. We present here an interesting family, which was thought to initially have an autosomal dominant skeletal dysplasia. Using a targeted sequencing skeletal dysplasia panel, the proband was found to be a compound heterozygote for two mutations in SLC26A2, one novel mutation, p.Ser522Phe and the other, the common mutation, p.Arg279Trp. In addition to the classical characteristics of MED, she presented with an atypical feature, bilateral synostoses between the 2nd and 3rd metatarsals. The parents were confirmed to be heterozygous for the two mutations but interestingly, the maternal grandfather, who had MED, was found to be homozygous for the common SLC26A2 mutation.