The <i>CAPN5</i> gene harbors a novel mutation in exon-6.

<p><b>A</b>. Chromatogram of proband showed a heterozygous c.750G>T DNA sequence mutation (arrow) in exon 6 of <i>CAPN5</i>. <b>B</b>. Calpain-5 is composed of four domains, and the mutation was located in catalytic domain IIb (green). <b>C</b>. Primary protein sequence alignment of calpain-5 orthologs shows high evolutionary conservation of the new mutated p.Lys250Asn residue, along with the two prior ADNIV mutations, p.Arg243Leu and p.Leu244Pro (red arrow/box) in catalytic domain IIb. The two previously identified ADNIV mutations and the newly identified ADNIV mutation are 2 to 9 amino acids upstream of the histidine catalytic residue (blue box). Amino acid mismatches are color-highlighted. <b>D</b>. Twelve human calpain family paralogs show the p.Lys250Asn is highly conserved. (Black, 100% similarity; dark grey, 80 to 100% similarity; light grey, 60 to 80% similarity; white, less than 60% similarity).