PMC6295682_01
Pedigree of a Canadian autosomal dominant brachydactyly type A1-affected family. The proband, as indicated by the black arrow, was the first patient ascertained. All red and blue shaded individuals represent those whose DNA samples were Sanger sequenced for the IHH variant (exon 1, c.285_287dupGAA, p.Glu95_Asn96insLys). The reddened squares (males) and circles (females) represent affected individuals with brachydactyly type A1 who carry the IHH variant. The blue coloured squares and circles indicate those who are unaffected by brachydactyly and do not carry the IHH variant. The green coloured squares and circles represent the individuals clinically diagnosed with brachydactyly whose DNA was not obtained or sequenced. Diagonal lines indicate deceased individuals.
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Seventeen additional family members were subsequently assessed, of whom 13 were clinically affected (Figure 1).
Chromosome location, gene structure, sequence analysis and protein structure of Indian Hedgehog. (a) Chromosome 2 and the location of the IHH gene drawn to scale. (b) The genomic DNA map for the IHH gene. (c) The mRNA for IHH with three numbered exons and the position of the mutation indicated. Electrophoretic tracings for the IHH variant for both unaffected and affected family members are also shown with the three-nucleotide codons, single-letter amino acid codes and corresponding numbered amino acid residues. (d) The IHH protein structure with key domains, regions, and the mutation indicated.. SS: signal sequence; SRR: sterol recognition region.
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A heterozygous IHH c.285_287dupGAA (p.Glu95_Asp96insLys) variant was detected (Figure 2) and validated using Sanger sequencing.