Figure 2

Missense mutations in ITPR1 in two families with autosomal dominant congenital nonprogressive spinocerebellar ataxia. A. Pedigree of Family C with AD CNPCA demonstrating segregation of the haplotype at 3pter with the disease (markers boxed in black). Affected individuals are represented by black symbols. A diagonal line indicates a deceased individual. Black arrow indicates the proband. B. Exome capture and massively parallel sequencing of III-6 from Family A identified a heterozygous mutation in ITPR1 (NM_001099952.2:c.4657G >A; p.Val1553Met) which was confirmed by Sanger sequencing. Sequence traces from an unaffected (top) and an affected member (bottom) of Family A show the heterozygous mutation c.4657G>A (red) in the affected individual. C. Multiple sequence alignment of Homo sapiens ITPR1 against its orthologues from ten other species (vertebrates are labeled in black; non-chordates are labeled in blue) was performed using ClustalW. The mutated amino acid (residue 1553 in the human sequence) is boxed in red. D. Sequence traces from an unaffected (top) and affected member (bottom) of Family C show the heterozygous mutation c.1804A >G (red) in the affected individual. E. Multiple sequence alignment of Homo sapiens ITPR1 against its orthologues from ten other species (vertebrates are labeled in black; non-chordates are labeled in blue) was performed using ClustalW. The mutated amino acid (residue 602 in the human sequence) is boxed in red.