Pyruvate carboxylase deficiency type A and type C: Characterization of five novel pathogenic variants inPCand analysis of the genotype–phenotype correlation

• DOI: 10.1002/humu.23742
• Publication Date: 2019-03-14T17:56:11Z
• Authors: Emanuele G. Coci; Vytautas Gapsys; Natasha Shur; Yoon Shin‐Podskarbi; Bert L. Groot; Kathryn Miller; Jerry Vockley; Neal Sondheimer; Rebecca Ganetzky; Peter Freisinger
• Keywords: Wild type; Genotype-phenotype distinction; Compound heterozygosity

Pyruvate carboxylase deficiency (PCD) is caused by biallelic mutations of the PC gene. The reported clinical spectrum includes a neonatal form with early death (type B), an infantile fatal A), and late-onset isolated mild intellectual delay C). Apart from homozygous stop-codon leading to type B PCD, genotype-phenotype correlation has not otherwise been discernible. Indeed, patients harboring heterozygous variants activity near zero can present either A or benign late onset C form. In this study, we analyzed six novel (three) compared them previously cases. First, observed that PCD associated in PC. silico modeling was used map former predict their potential effects on enzyme structure function. We found lead phenotype based destabilization between two major conformers. general, our study improves overall understanding PCD.