One NF1 Mutation may Conceal Another

Genes

Hélène Dollfus¹  Diana Rodriguez²  Catherine Yardin³  Benjamin Dauriat³  Christian Derancourt⁴  Quentin Thomas⁵  Laurence Faivre⁵  Ingrid Laurendeau⁶  Yvon-Gauthier Muller⁷  Audrey Briand-Suleau⁸  Béatrice Parfait⁸  Audrey Coustier⁸  Dominique Vidaud⁸  Théodora Mayard⁸  Laurence Pacot⁸  Eric Pasmant⁸  Camille Tlemsani⁸  Cyril Burin des Roziers⁸  Michel Vidaud⁸  Sophie Blesson⁹  Brigitte Gilbert-Dussardier^1,10 

[1] Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil, 67091 Strasbourg, France;Department of Child Neurology and National Reference Center for Neurogenetic Disorders, Armand Trousseau Hospital, GHUEP, AP-HP, INSERM U1141, 75012 Paris, France;Department of Cytogenetics and clinical genetics, Limoges University Hospital, 87042 Limoges, France;EA 4537, Antilles University, 97261 Fort-de-France, Martinique, France;Inserm, UMR 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21079 Dijon, France;Institut Cochin, INSERM U1016, Université Paris Descartes, 75014 Paris, France;Service de Génétique Médicale, Hôpital de Hautepierre, 67200 Strasbourg, France;Service de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France;Service de Génétique, CHRU de Tours, 37044 Tours, France;Service de Génétique, EA3808, Université de Poitiers, CHU de Poitiers, 86000 Poitiers, France;

关键词: de novo variant;    Legius syndrome;    neurofibromatosis type 1;    NF1;    SPRED1;   

DOI  :  10.3390/genes10090633

来源: DOAJ

【 摘 要 】

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 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.

【 授权许可】

Unknown