ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.
ENPP1 deficiency
autosomal recessive hypophosphatemic rickets type 2 (ARHR2)
bone/Joint abnormalities
database
generalized arterial calcification of infancy (GACI)
genotype-phenotype correlations
monoallelic ENPP1
rare variants
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
16
09
2022
received:
16
03
2022
accepted:
21
09
2022
pubmed:
24
9
2022
medline:
15
12
2022
entrez:
23
9
2022
Statut:
ppublish
Résumé
Loss-of-function variants in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) cause ENPP1 Deficiency, a rare disorder characterized by pathological calcification, neointimal proliferation, and impaired bone mineralization. The consequence of ENPP1 Deficiency is a broad range of age dependent symptoms and morbidities including cardiovascular complications and 50% mortality in infants, autosomal recessive hypophosphatemic rickets type 2 (ARHR2) in children, and joint pain, osteomalacia and enthesopathies in adults. Recent research continues to add to the growing clinical presentation profile as well as expanding the role of ENPP1 itself. Here we review the current knowledge on the spectrum of clinical and genetic findings of ENPP1 Deficiency reported in patients diagnosed with GACI or ARHR2 phenotypes using a comprehensive database of known ENPP1 variants with associated clinical data. A total of 108 genotypes were identified from 154 patients. Of the 109 ENPP1 variants reviewed, 72.5% were demonstrably disease-causing, a threefold increase in pathogenic/likely pathogenic variants over other databases. There is substantial heterogeneity in disease severity, even among patients with the same variant. The approach to creating a continuously curated database of ENPP1 variants accessible to clinicians is necessary to increase the diagnostic yield of clinical genetic testing and accelerate diagnosis of ENPP1 Deficiency.
Substances chimiques
Phosphoric Diester Hydrolases
EC 3.1.4.-
Pyrophosphatases
EC 3.6.1.-
ectonucleotide pyrophosphatase phosphodiesterase 1
EC 3.1.4.1
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1673-1705Informations de copyright
© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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