RESUMO
Background: Wolfram syndrome (WFS) is an autosomal recessive disorder that often leads to diabetes, optic atrophy, and sensorineural hearing loss. The aim of this study was to determine the clinical characteristics and the genetic cause of the first two Moroccan families presenting with WFS. Methods: The clinical features of five members of two WFS families were evaluated. Whole-exome sequencing was conducted to explore the underlying genetic cause in the affected patients. Results: Two homozygous variants in the WFS1 gene were identified, each in one of the two families studied: a missense c.1329C>G variant (p.Ser443Arg) and a nonsense mutation c.1113G>A (p.Trp371Ter). These variants affected conserved amino acid residues, segregated well in the two families, and are absent from genetic databases and in controls of Moroccan origin. Bioinformatics analysis classified the two variants as pathogenic by in silico tools and molecular modeling. Conclusion: Our study identified for the first time two variants in Moroccan patients with WFS that extends the mutational spectrum associated with the disease.
Assuntos
Proteínas de Membrana , Mutação de Sentido Incorreto , Linhagem , Síndrome de Wolfram , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Códon sem Sentido/genética , Sequenciamento do Exoma/métodos , Homozigoto , Proteínas de Membrana/genética , Marrocos , Mutação , Mutação de Sentido Incorreto/genética , Síndrome de Wolfram/genética , Adulto JovemRESUMO
At the request of the authors, the names of the authors should be as follow: Abida N, Tibar H, Boudhas A, Oumerzouk J, Bourazza A.
