Amerindian pyruvate carboxylase deficiency is associated with two distinct missense mutations

作者：Carbone MA; MacKay N; Ling MF; Cole DEC; Douglas C; Rigat B; Feigenbaum A; Clarke JTR; Haworth JC; Greenberg CR; Seargeant L; Robinson BH^*

来源：American Journal of Human Genetics, 1998, 62(6): 1312-1319.

DOI：10.1086/301884

We characterized the pyruvate carboxylase (PC) gene by PCR amplification, subcloning, and sequencing. The coding region has 19 exons and 18 introns spanning similar to 16 kb of genomic DNA. Screening both the cDNA and the gene of individuals with the simple A form of PC deficiency revealed an 1828G-->A missense mutation in 11 Ojibwa and 2 Cree patients and 2229G-->T transversion mutation in 2 brothers of Micmac origin. Carrier frequency may be as high as 1/10 in some groupings. The two point mutations are located in a region of homology conserved among yeast, rat, and human PC, in the vicinity of the carboxylation domain of the enzyme. These data provide the first characterization of the human PC gene structure, the identification of common pathogenic mutations, and the demonstration of a founder effect in the Ojibwa and Cree patients.

• 出版日期1998-6