Further Evidence for the Implication of the MET Gene in Non-Syndromic Autosomal Recessive Deafness
| Autor: | Amina Bakhchane, Khalid Snoussi, Crystel Bonnet, Christine Petit, Amale Bousfiha, Hicham Charoute, Zied Riahi, Abdelhamid Barakat, Lamiae Elkhattabi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Genetics
0303 health sciences Daughter Hearing loss Sema domain media_common.quotation_subject 030305 genetics & heredity Mutant Biology 3. Good health 03 medical and health sciences Mutation (genetic algorithm) otorhinolaryngologic diseases medicine Mesenchymal–epithelial transition Missense mutation medicine.symptom Gene Genetics (clinical) 030304 developmental biology media_common |
| Zdroj: | Human Heredity. 84:109-116 |
| ISSN: | 1423-0062 0001-5652 |
| Popis: | Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified a novel homozygous missense mutation in the METgene causing a non-syndromic hearing impairment DFNB97 form. Whole-exome sequencing was performed to determine the genetic causes of hearing loss in a Moroccan consanguineous family with an affected daughter. The structural analysis of native and mutant in the SEMA domain of the MET receptor was investigated using a molecular dynamics simulation (MDS) approach. We identified a novel pathogenic homozygous c.948A>G (p.Ile316Met) mutation in the MET gene in one deaf Moroccan young girl carrying a total bilateral non-syndromic hearing impairment. The results of the MDS approach show that an Ile316Met mutation in the SEMA domain leads to protein flexibility loss. This may produce a major impact on the structural conformation of the MET receptor, which also affects the function and binding site of the receptor. This is the first time that a mutation in the MET gene is described in a Moroccan family. Moreover, this study reports the second family in the world associating deafness and mutation in the MET gene. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|