title: A novel MT-CO1 m.6498C>A variation associated with the m.7444G>A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes in a patient with hearing impairment, diabetes and congenital visual loss.
abstract: Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. Sensorineural hearing loss (SNHL) has been described in association to different mitochondrial multisystem syndromes, often involving the central nervous system, neuromuscular, or endocrine organs. In this study, we described a Tunisian young girl with hearing impairment, congenital visual loss and maternally inherited diabetes. No mutation was found in the mitochondrial tRNA(Leu(UUR)) and the 12S rRNA genes. However, we detected the m.7444G>A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes. This mutation eliminates the termination codon of the MT-CO1 gene and extends the COI polypeptide by three amino acids (Lys-Gln-Lys) to the C-terminal. The whole mitochondrial genome screening revealed the presence of a novel mutation m.6498C>A (L199I) in the mitochondrial DNA-encoded subunit I of the cytochrome c oxidase (COX). This "probably damaging" transversion affects a highly conserved domain and it was absent in 200 Tunisian controls. The studied patient was classified under the haplogroup H2a.
authors.affiliation: Faculty of Medicine of Sfax, Human Molecular Genetic Laboratory, University of Sfax, Tunisia. emna_mkaouar@mail2world.com
authors.forename: Emna
authors.initials: E
authors.lastname: Mkaouar-Rebai
authors.forename: Imen
authors.initials: I
authors.lastname: Chamkha
authors.forename: Thouraya
authors.initials: T
authors.lastname: Kammoun
authors.forename: Olfa
authors.initials: O
authors.lastname: Alila-Fersi
authors.forename: Hajer
authors.initials: H
authors.lastname: Aloulou
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D018388:Codon, Terminator / Q000235:genetics*; D054062:Deaf-Blind Disorders / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D012362:RNA, Transfer, Ser / Q000235:genetics*; D014416:Tunisia
chemical_list: D018388:Codon, Terminator; D012362:RNA, Transfer, Ser; D003576:Electron Transport Complex IV; C581860:cytochrome c oxidase subunit I, human