Identification of the first homozygous intragenic deletion in the YY1AP1 gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome.

Fiche publication

Date publication

septembre 2023

Journal

American journal of medical genetics. Part A

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence , Pr PHILIPPE Christophe , Mr DUFFOURD Yannis , Pr THAUVIN-ROBINET Christel , Dr ALBUISSON Juliette

Tous les auteurs :
Viora-Dupont E, Denommé-Pichon A, Chevarin M, Patat O, Willems M, Bourgon N, Bruel A, Aubert-Mucca M, Galinier M, Itier R, Decramer S, Piton A, Gerard B, Billon C, Jeunemaitre X, Duffourd Y, Callier P, Thauvin C, Philippe C, Faivre L, Albuisson J, Vitobello A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/37698238

Résumé

Grange syndrome (GRNG-MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in YY1AP1. In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16 months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array-CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out-of-frame deletion of 1.84 kb encompassing exons seven and eight of YY1AP1, confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.