One Mutation may Conceal Another.
Fiche publication
Date publication
août 2019
Journal
Genes
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
Pacot L, Burin des Roziers C, Laurendeau I, Briand-Suleau A, Coustier A, Mayard T, Tlemsani C, Faivre L, Thomas Q, Rodriguez D, Blesson S, Dollfus H, Muller YG, Parfait B, Vidaud M, Gilbert-Dussardier B, Yardin C, Dauriat B, Derancourt C, Vidaud D, Pasmant E
Lien Pubmed
Résumé
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the gene, a negative regulator of the RAS-MAPK pathway. The gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the and genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent variants. All variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the gene from her mother and carried a variant of unknown significance in the gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease.
Mots clés
Legius syndrome, NF1, SPRED1, de novo variant, neurofibromatosis type 1
Référence
Genes (Basel). 2019 Aug 22;10(9):