TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Journal of Medical Genetics Année : 2023

TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype

Résumé

The TRAPP (TRAfficking Protein Particle) complexes are evolutionarily conserved tethering factors involved in the intracellular transport of vesicles for secretion and autophagy processes. Pathogenic variants in 8 genes (of 14) encoding TRAPP proteins are involved in ultra-rare human diseases, called TRAPPopathies. Seven of them are autosomal recessive neurodevelopmental disorders with overlapping phenotypes. Since 2018, two homozygous missense variants in TRAPPC2L have been reported in five individuals from three unrelated families with early-onset and progressive encephalopathy, with episodic rhabdomyolysis. We now describe the first pathogenic protein-truncating variant in the TRAPPC2L gene found at a homozygous state in two affected siblings. This report provides key genetic evidence invaluable to establishing the gene-disease relationship for this gene and important insights into the TRAPPC2L phenotype. Regression, seizures and postnatal microcephaly initially described are not constant features. Acute episodes of infection do not contribute to the neurological course. HyperCKaemia is part of the clinical picture. Thus, TRAPPC2L syndrome is mainly characterised by a severe neurodevelopmental disorder and a variable degree of muscle involvement, suggesting that it belongs to the clinical entity of rare congenital muscular dystrophies.

Domaines

Génétique
Fichier principal
Vignette du fichier
TRAPPC2L-jmedgenet-2023.pdf (508.61 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04254101 , version 1 (27-11-2023)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Mario Abaji, Cecile Mignon-Ravix, Svetlana Gorokhova, Pierre Cacciagli, Jeremie Mortreux, et al.. TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype. Journal of Medical Genetics, 2023, ⟨10.1136/jmg-2022-108677⟩. ⟨hal-04254101⟩
53 Consultations
21 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More