title: Modification of human hearing loss by plasma-membrane calcium pump PMCA2.
abstract: Five adult siblings presented with autosomal recessive sensorineural hearing loss: two had high-frequency loss, whereas the other three had severe-to-profound loss affecting all frequencies. Genetic evaluation revealed that a homozygous mutation in CDH23 (which encodes cadherin 23) caused the hearing loss in all five siblings and that a heterozygous, hypofunctional variant (V586M) in plasma-membrane calcium pump PMCA2, which is encoded by ATP2B2, was associated with increased loss in the three severely affected siblings. V586M was detected in two unrelated persons with increased sensorineural hearing loss, in the other caused by a mutation in MYO6 (which encodes myosin VI) in one and by noise exposure, suggesting that this variant may modify the severity of sensorineural hearing loss caused by a variety of factors.
authors.affiliation: Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md 20850, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Schultz
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yang
authors.forename: Ariel J
authors.initials: AJ
authors.lastname: Caride
authors.forename: Adelaida G
authors.initials: AG
authors.lastname: Filoteo
authors.forename: Alan R
authors.initials: AR
authors.lastname: Penheiter
authors.forename: Ayala
authors.initials: A
authors.lastname: Lagziel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
authors.forename: Saidi A
authors.initials: SA
authors.lastname: Mohiddin
authors.forename: Lameh
authors.initials: L
authors.lastname: Fananapazir
authors.forename: Anne C
authors.initials: AC
authors.lastname: Madeo
authors.forename: John T
authors.initials: JT
authors.lastname: Penniston
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D000328:Adult; D000483:Alleles; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D027682:Cation Transport Proteins; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000145:classification / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D053499:Plasma Membrane Calcium-Transporting ATPases; D017354:Point Mutation; D035781:Siblings
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D027682:Cation Transport Proteins; D053499:Plasma Membrane Calcium-Transporting ATPases; C506958:ATP2B2 protein, human; D000252:Calcium-Transporting ATPases