title: TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss.
abstract: Nonsyndromic genetic deafness is highly heterogeneous in its clinical presentation, pattern of inheritance and underlying genetic causes. Mutations in TMPRSS3 gene encoding transmembrane serine protease account for <1 % of autosomal recessive nonsyndromic hearing loss (ARNSHL) in Caucasians. Targeted next generation sequencing in the index family with profound deaf parents and a son, and Sanger sequencing of selected TMPRSS3 gene regions in a cohort of thirty-five patients with suspected ARNSHL was adopted. A son and his mother in the index family were homozygous for TMPRSS3 c.208delC (p.His70Thrfs*19) variant. Father was digenic compound heterozygote for the same variant and common GJB2 c.35delG variant. Three additional patients from the ARNSHL cohort were homozygous for TMPRSS3 c.208delC. TMPRSS3 defects seem to be an important cause of ARNSHL in Slovenia resulting in uniform phenotype with profound congenital hearing loss, and satisfactory hearing and speech recognition outcome after cochlear implantation. Consequently, TMPRSS3 gene analysis should be included in the first tier of genetic investigations of ARNSHL along with GJB2 and GJB6 genes.
authors.affiliation: Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloska 2, Ljubljana, Slovenia.|Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
authors.forename: Saba
authors.initials: S
authors.lastname: Battelino
authors.affiliation: University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, SI-1252, Ljubljana, Slovenia.
authors.forename: Gasper
authors.initials: G
authors.lastname: Klancar
authors.affiliation: University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, SI-1252, Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Kovac
authors.affiliation: Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.|University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, SI-1252, Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.affiliation: Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia. katarina.trebusak@kclj.si.|University Medical Centre Ljubljana, University Children's Hospital, Bohoriceva 20, SI-1252, Ljubljana, Slovenia. katarina.trebusak@kclj.si.
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebusak Podkrajsek
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003638:Deafness / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D012697:Serine Endopeptidases / Q000235:genetics*; D017524:Slovenia; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human
keywords: Autosomal recessive nonsyndromic hearing loss; Next generation sequencing; TMPRSS3