title: Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families.
abstract: Two genes for components of the mitochondrial translational apparatus, mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) lie adjacent to one another on human chromosome 19, within the critical interval for the autosomal dominant deafness locus DFNA4. Both genes are plausible candidates for DFNA4, based on the fact that deafness mutations in mtDNA have been mapped both to tRNA-ser(UCN) and to the accuracy domain of the small subunit rRNA. We have sequenced the coding regions, proximal promoters, 5' and 3' UTR and splice junctional regions of both genes in two families with DFNA4-linked deafness and in controls. Novel polymorphisms 84425C>T, 83907A>G, 79485T>G, 79406C>T, 71755A>C and 68686C>G (numbered as in GenBank AC011455) were found in one or both families, but none is a plausible disease-causing mutation. Although regulatory mutations affecting either gene could still be involved in the phenotype, structural gene mutations affecting SARSM or RPMS12 can be excluded from consideration as the cause of DFNA4-linked deafness, at least in the families identified thus far.
authors.affiliation: Institute of Medical Technology, University of Tampere & Tampere University Hospital, Finland.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Shah
authors.forename: M
authors.initials: M
authors.lastname: Toompuu
authors.forename: T
authors.initials: T
authors.lastname: Hakkinen
authors.forename: A T
authors.initials: AT
authors.lastname: Rovio
authors.forename: C
authors.initials: C
authors.lastname: van Ravenswaay
authors.forename: E M
authors.initials: EM
authors.lastname: De Leenheer
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
authors.forename: C W
authors.initials: CW
authors.lastname: Cremers
authors.forename: H T
authors.initials: HT
authors.lastname: Jacobs
mesh_terms: D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005190:Family; D005799:Genes, Dominant / Q000235:genetics*; D006367:HeLa Cells; D006319:Hearing Loss, Sensorineural / Q000151:congenital / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D009426:Netherlands; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics*; D012714:Serine-tRNA Ligase / Q000235:genetics*; D014481:United States
chemical_list: D017931:DNA Primers; D021901:DNA, Intergenic; D022821:RNA Splice Sites; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C034212:ribosomal protein S12; D012714:Serine-tRNA Ligase