title: Mutational screening in patients with profound sensorineural hearing loss and neurodevelopmental delay: Description of a novel m.3861A > C mitochondrial mutation in the MT-ND1 gene.
abstract: Mitochondrial diseases caused by mitochondrial dysfunction are a clinically and genetically, heterogeneous group of disorders involving multiple organs, particularly tissues with high-energy demand. Hearing loss is a recognized symptom of a number of mitochondrial diseases and can result from neuronal or cochlear dysfunction. The tissue affected in this pathology is most probably the cochlear hair cells, which are essential for hearing function since they are responsible for maintaining the ionic gradients necessary for sound signal transduction. Several mitochondrial DNA mutations have been associated with hearing loss and since mitochondria are crucial for the cellular energy supply in many tissues, most of these mtDNA mutations affect several tissues and will cause syndromic hearing loss. In the present study, we described 2 patients with sensorineural hearing loss and neurodevelopmental delay in whom we tested mitochondrial genes described to be associated with syndromic hearing loss. One of these patients showed a novel heteroplasmic mitochondrial mutation m.3861A > C (W185C) which lead to a loss of stability of the ND1 protein since it created a new hydrogen bund between the unique created cystein C185 and the A182 residue. In the second patient, we detected two novel heteroplasmic variations m.12350C > A (T5N) and m.14351T > C (E108G) respectively in the MT-ND5 and the MT-ND6 genes. The TopPred II prediction for the E108G variation revealed a decrease of the hydrophobicity in the mutated MT-ND6.
authors.affiliation: Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Ammar
authors.affiliation: Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabebi
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Sfaihi
authors.affiliation: Department of Life Sciences, Faculty of Sciences of Sfax, University of Sfax, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Alila-Fersi
authors.affiliation: Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Maalej
authors.affiliation: Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Rahma
authors.initials: R
authors.lastname: Felhi
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Chabchoub
authors.affiliation: Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Tunisia.
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.affiliation: Department of Life Sciences, Faculty of Sciences of Sfax, University of Sfax, Tunisia.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
authors.affiliation: Department of Life Sciences, Faculty of Sciences of Sfax, University of Sfax, Tunisia. Electronic address: emna.mkaouar@gmail.com.
authors.forename: Emna
authors.initials: E
authors.lastname: Mkaouar-Rebai
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics*; D065886:Neurodevelopmental Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human
keywords: Hearing loss; MT-ND1; Mitochondrial mutations; m.3861A > C; mtDNA