Format

Send to

Choose Destination
Eur J Hum Genet. 2018 Mar;26(3):340-349. doi: 10.1038/s41431-017-0087-x. Epub 2018 Jan 12.

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

Author information

1
Service de Réanimation Néonatale, Pole Femme-Mère-Enfant, CH Felix Guyon, CHU de La Réunion, Saint-Denis, La Réunion, France. jean-luc.alessandri@chu-reunion.fr.
2
Laboratory of embryology and genetics of congenital malformations, INSERM UMR 1163, Institut Imagine, Paris, France.
3
Institut Imagine, Paris Descartes-Sorbonne Paris Cité University, Paris, France.
4
Unité de Génétique Médicale, Pole Femme-Mère-Enfant, Groupe Hospitalier Sud Réunion, CHU de La Réunion, La Réunion, France.
5
Service de Génétique, UFR Santé Caen, Caen, France.
6
Centre de Recherche du CHU Sainte-Justine et Université de Montréal, Montréal, QC, Canada.
7
Service de Gynécologie-Obstétrique, CH Mamoudzou, Mayotte, France.
8
INSERM UMR 1231 GAD team, Genetics of Developmental Anomalies, Université de Bourgogne-Franche Comté, Dijon, France.
9
FHU-TRANSLAD, Université de Bourgogne/CHU, Dijon, France.
10
Service de Gynécologie-Obstétrique, Pole Femme-mère-Enfant, Groupe Hospitalier Sud Réunion, CHU de La Réunion, La Réunion, France.
11
Genomic Platform, INSERM UMR 1163, Institut Imagine, Paris, France.
12
Bioinformatic Platform, INSERM UMR 1163, Institut Imagine, Paris, France.
13
Service de Réanimation Néonatale, Pole Femme-Mère-Enfant, CH Felix Guyon, CHU de La Réunion, Saint-Denis, La Réunion, France.
14
Service de Génétique, CH Félix Guyon, CHU de La Réunion, La Réunion, France.
15
Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.
16
Centre de Génétique, Hôpital Couple-Enfant, CHU de Grenoble-Alpes, 38700, La Tronche, France.

Abstract

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.

PMID:
29330547
PMCID:
PMC5839001
DOI:
10.1038/s41431-017-0087-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center