title: A genetic basis for mechanosensory traits in humans.
abstract: In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.
authors.affiliation: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Frenzel
authors.forename: Jörg
authors.initials: J
authors.lastname: Bohlender
authors.forename: Katrin
authors.initials: K
authors.lastname: Pinsker
authors.forename: Bärbel
authors.initials: B
authors.lastname: Wohlleben
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Lechner
authors.forename: Daniela
authors.initials: D
authors.lastname: Schiska
authors.forename: Teresa
authors.initials: T
authors.lastname: Jaijo
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.forename: Manfred
authors.initials: M
authors.lastname: Gross
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017704:Baroreflex; D015331:Cohort Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D040542:Mechanotransduction, Cellular; D009154:Mutation; D010641:Phenotype; D013696:Temperature; D014110:Touch / Q000235:genetics*; D052245:Usher Syndromes / Q000235:genetics*; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human