Figure 2.

Recessive missense mutations in SERPINH1 change a highly conserved HSP47 residue. (A) Pedigree of the family showing two of four affected siblings (R92-020A and B) and a phenotypically undescribed miscarriage. (B) Chromatograms showing the sequence of position c. 710 in SERPINH1 (in yellow) annotated as a thymine (T) in the WT allele and cytosine (C) in R92-020A and the carrier parents. (C) Representation of HSP47 protein with the serine-type endopeptidase inhibitor domain in light blue. Protein alignment of HSP47 sequences from several vertebrate species show high conservation of the residues with OI-related mutations. The R92-020A mutation, resulting in the missense change at amino acid 237, is labeled with a black box and arrow. The previously described human OI case with a missense mutation in another highly conserved residue (L87) is shown in blue, and the dachshund (dog) OI change at residue 326L is shown in green.