Mutations in PRDM5 Cause Brittle Cornea Syndrome
(A) Autozygosity mapping by SNP6.0 array demonstrates homozygosity at 4q28 in affected members of families BCS-001 (individuals IV:4, IV:6, and IV:9) and BCS-002 (individual V:5).
(B) Nullizygosity for 34 adjacent SNPs within the autozygous region demonstrates a homozygous 52.46 kb deletion encompassing exons 9–14 of PRDM5 in individual IV:5 of family BCS-001. This in-frame deletion and further mutations in PRDM5 identified are shown.
(C) Schematic of PRDM5 protein showing N-terminal PR-SET domain and 16 zinc fingers toward the C terminus. Missense mutation p.Tyr107Cys is within the PR-SET domain in a sequence of highly conserved amino acid residues. Nonsense mutation p.Arg590X predicts a truncated protein, resulting in loss of zinc fingers 15 and 16, whereas deletion of exons 9–14 predicts loss of zinc fingers 6–13.