Genes, Vol. 10, Pages 633: One NF1 Mutation may Conceal Another

Genes, Vol. 10, Pages 633: One NF1 Mutation may Conceal Another Genes doi: 10.3390/genes10090633 Authors: Laurence Pacot Cyril Burin des Roziers Ingrid Laurendeau Audrey Briand-Suleau Audrey Coustier Théodora Mayard Camille Tlemsani Laurence Faivre Quentin Thomas Diana Rodriguez Sophie Blesson Hélène Dollfus Yvon-Gauthier Muller Béatrice Parfait Michel Vidaud Brigitte Gilbert-Dussardier Catherine Yardin Benjamin Dauriat Christian Derancourt Dominique Vidaud Eric Pasmant 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 NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 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 NF1 and SPRED1 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 NF1 variants. All NF1 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 NF1 gene from her mother and carried a variant of unknown significance in the SPRED1...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research