Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma

Autor: Douglas Ralph, Michael A. Levine, Gabriele Richard, Michelle M. Morrow, Elizabeth K. Flynn, Jouni Uitto, Qiaoli Li
Rok vydání: 2022
Předmět:
Zdroj: Human Mutation. 43:1183-1200
ISSN: 1098-1004
1059-7794
Popis: ENPP1 encodes ENPP1, an ectonucleotidase catalyzing hydrolysis of ATP to AMP and inorganic pyrophosphate (PPi), and an endogenous plasma protein physiologically preventing ectopic calcification of connective tissues. Mutations in ENPP1 have been reported in association with a range of human genetic diseases. In this mutation update, we provide a comprehensive review of all the pathogenic variants, likely pathogenic variants, and variants of unknown significance in ENPP1 associated with three autosomal recessive disorders-generalized arterial calcification of infancy (GACI), autosomal recessive hypophosphatemic rickets type 2 (ARHR2), and pseudoxanthoma elasticum (PXE), as well as with a predominantly autosomal dominant disorder-Cole disease. The classification of all variants is determined using the latest ACMG guidelines. A total of 140 ENPP1 variants were curated consisting of 133 previously reported variants and seven novel variants, with missense variants being the most prevalent (70.0%, 98/140). While the pathogenic variants are widely distributed in the ENPP1 gene of patientsgen without apparent genotype-phenotype correlation, eight out of nine variants associated with Cole disease are confined to the somatomedin-B-like (SMB) domains critical for homo-dimerization of the ENPP1 protein.
Databáze: OpenAIRE
Externí odkaz: