title: Haplogroup analysis supports a pathogenic role for the 7510T>C mutation of mitochondrial tRNA(Ser(UCN)) in sensorineural hearing loss.
abstract: We ascertained a large North American family, LMG309, with matrilineal transmission of non-syndromic, progressive sensorineural hearing loss (SNHL). There was no history of aminoglycoside exposure, and penetrance was complete. We sequenced the entire mitochondrial genome and identified the previously reported 7510T>C transition in the tRNA(Ser(UCN)) gene. The 7510T>C was homoplasmic in all affected members. The LMG309 mitochondrial sequence belongs to an unnamed subgroup of mitochondrial haplogroup H. We demonstrate that the previously reported Spanish family S258 carries 7510T>C on a different mitochondrial sub-haplogroup, H1. We did not detect 7510T>C among 79 Caucasian haplogroup H control samples, including 11 from sub-haplogroup H1 and one from the same sub-haplogroup as LMG309. Our results provide strong genetic evidence that 7510T>C is a pathogenic mutation that causes non-syndromic SNHL.
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850-3320, USA.
authors.forename: V
authors.initials: V
authors.lastname: Labay
authors.forename: G
authors.initials: G
authors.lastname: Garrido
authors.forename: A C
authors.initials: AC
authors.lastname: Madeo
authors.forename: W E
authors.initials: WE
authors.lastname: Nance
authors.forename: T B
authors.initials: TB
authors.lastname: Friedman
authors.forename: P L
authors.initials: PL
authors.lastname: Friedman
authors.forename: I
authors.initials: I
authors.lastname: Del Castillo
authors.forename: A J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D005192:Family Health; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D009656:North America; D010375:Pedigree; D017354:Point Mutation; D012362:RNA, Transfer, Ser / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser