Families with novel mutations in the PQBP1 gene. A, Partial pedigree of the family described by Renpenning and colleagues (1962) (family K8110), with the c.641insC mutation. Numbering of the pedigree is consistent with that published elsewhere (Stevenson et al. 1998). The c.641insC mutation, highlighted and indicated by the arrow, is present in exon 5 and is very close to the exon/intron boundary. The shaded region shows the intronic sequence. This mutation causes a frameshift in the C2 domain, resulting in the premature truncation of the protein. B, Pedigree of family K9008, with the c.575_576delAG mutation in the NLS (nuclear localization signal) domain. This deletion is in exon 4 (highlighted in yellow) and occurs very close to the exon/intron boundary (sequence contributed from the intron is shaded). This mutation causes a frameshift and results in a premature truncation of the PQBP1 protein, which lacks the C2 domain.

Truncating mutations in the PQBP1 protein. This figure shows the structure of the PQBP1 protein with the WW domain, the PRD with DR/ER repeats, the NLS domain, and the C2 domain (modified from Waragai et al. 1999). The novel mutations reported in this study (c.575_576delAG and c.641insC) are in boldface. The three different mutations in the DR/ER domain reported by Kalscheuer et al. (2003) are in italics.