Sara Salime1, Majida Charif2, Amale Bousfiha3, Soukaina Elrharchi3, Amina Bakhchane3, Hicham Charoute3, Mostafa Kabine4, Khalid Snoussi3, Guy Lenaers2, Abdelhamid Barakat5. 1. Human Molecular Genetics Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Laboratoire de santé et Environnement, Université Hassan II, Faculté des Sciences Aïn Chock, Casablanca, Morocco. 2. MitoLab Team, CNRS UMR6015, INSERM U1083, Université d'Angers, CHU Bât IRIS/IBS, Rue des Capucins, 49933 Angerscedex 9, France. 3. Human Molecular Genetics Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco. 4. Laboratoire de santé et Environnement, Université Hassan II, Faculté des Sciences Aïn Chock, Casablanca, Morocco. 5. Human Molecular Genetics Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco. Electronic address: hamid.barakat@pasteur.ma.
Abstract
OBJECTIVES: Autosomal recessive non-syndromic hearing loss is a heterogeneous disorder and the most prevalent human genetic sensorineural defect. In this study, we investigated the geneticcause of sensorineural hearing loss in Moroccan patients and presented the importance of whole exome sequencing (WES) to identify candidate genes in two Moroccan families with profound deafness. METHODS: After excluding mutations previously reported in Moroccan deaf patients, whole exome sequencing was performed and Sanger sequencing was used to validate mutations in these genes. RESULTS: Our results disclosed the c.113_114insT (p.Lys41GlufsX8) and c.406C > T (p.Arg130X) homozygous mutations in PJVK and a homozygous c.5203C > T (p.Arg1735Trp) mutation in MYO15A, both genes responsible for non-syndromic recessive hearing loss DFNB59 and DFNB3, respectively. CONCLUSION: We identified in Moroccan deaf patients two mutations in PJVK and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss. These results emphasize that whole exome sequencing is a powerful diagnostic strategy to identify pathogenic mutations in heterogeneous disorders with many various causative genes.
OBJECTIVES:Autosomal recessive non-syndromic hearing loss is a heterogeneous disorder and the most prevalent human genetic sensorineural defect. In this study, we investigated the geneticcause of sensorineural hearing loss in Moroccan patients and presented the importance of whole exome sequencing (WES) to identify candidate genes in two Moroccan families with profound deafness. METHODS: After excluding mutations previously reported in Moroccan deaf patients, whole exome sequencing was performed and Sanger sequencing was used to validate mutations in these genes. RESULTS: Our results disclosed the c.113_114insT (p.Lys41GlufsX8) and c.406C > T (p.Arg130X) homozygous mutations in PJVK and a homozygous c.5203C > T (p.Arg1735Trp) mutation in MYO15A, both genes responsible for non-syndromic recessive hearing loss DFNB59 and DFNB3, respectively. CONCLUSION: We identified in Moroccan deaf patients two mutations in PJVK and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss. These results emphasize that whole exome sequencing is a powerful diagnostic strategy to identify pathogenic mutations in heterogeneous disorders with many various causative genes.
Authors: Tiantian Du; Jie Gao; Peilong Li; Yunshan Wang; Qiuchen Qi; Xiaoyan Liu; Juan Li; Chuanxin Wang; Lutao Du Journal: Clin Transl Med Date: 2021-08
Authors: Ambroise Wonkam; Samuel Mawuli Adadey; Isabelle Schrauwen; Elvis Twumasi Aboagye; Edmond Wonkam-Tingang; Kevin Esoh; Kalinka Popel; Noluthando Manyisa; Mario Jonas; Carmen deKock; Victoria Nembaware; Diana M Cornejo Sanchez; Thashi Bharadwaj; Abdul Nasir; Jenna L Everard; Magda K Kadlubowska; Liz M Nouel-Saied; Anushree Acharya; Osbourne Quaye; Geoffrey K Amedofu; Gordon A Awandare; Suzanne M Leal Journal: Commun Biol Date: 2022-04-19
Authors: María Domínguez-Ruiz; Montserrat Rodríguez-Ballesteros; Marta Gandía; Elena Gómez-Rosas; Manuela Villamar; Pietro Scimemi; Patrizia Mancini; Nanna D Rendtorff; Miguel A Moreno-Pelayo; Lisbeth Tranebjaerg; Carme Medà; Rosamaria Santarelli; Ignacio Del Castillo Journal: Genes (Basel) Date: 2022-01-15 Impact factor: 4.096