Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Réunion Island, in patients with Fryns syndrome.

Date publication

mars 2018

Journal

European journal of human genetics : EJHG

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence , Pr KUENTZ Paul

Tous les auteurs :
Alessandri JL, Gordon CT, Jacquemont ML, Gruchy N, Ajeawung NF, Benoist G, Oufadem M, Chebil A, Duffourd Y, Dumont C, Gérard M, Kuentz P, Jouan T, Filippini F, Nguyen TTM, Alibeu O, Bole-Feysot C, Nitschké P, Omarjee A, Ramful D, Randrianaivo H, Doray B, Faivre L, Amiel J, Campeau PM, Thevenon J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29330547

Résumé

Fryns syndrome (FS) is a multiple malformations syndrome with major features of congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, and a range of other lower frequency malformations. FS is typically lethal in the fetal or neonatal period. Inheritance is presumed autosomal recessive. Although no major genetic cause has been identified for FS, biallelic truncating variants in PIGN, encoding a component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, have been identified in a limited number of cases with a phenotype compatible with FS. Biallelic variants in PIGN, typically missense or compound missense with truncating, also cause multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Here we report six further patients with FS with or without congenital diaphragmatic hernia and recessive loss of function PIGN alleles, including an intragenic deletion with a likely founder effect in La Réunion and other Indian Ocean islands. Our results support the hypothesis that a spectrum of phenotypic severity is associated with recessive PIGN variants, ranging from FS at the extreme end, caused by complete loss of function, to MCAHS1, in which some residual PIGN function may remain. Our data add FS resulting from PIGN variants to the catalog of inherited GPI deficiencies caused by the disruption of the GPI-anchor biosynthesis pathway.

Mots clés

Facies, Female, Founder Effect, Gene Deletion, Hernia, Diaphragmatic, genetics, Humans, Infant, Infant, Newborn, Limb Deformities, Congenital, genetics, Loss of Function Mutation, Male, Phosphotransferases, genetics

Référence

Eur. J. Hum. Genet.. 2018 Mar;26(3):340-349