title: Mutations of GIPC3 cause nonsyndromic hearing loss DFNB72 but not DFNB81 that also maps to chromosome 19p.
abstract: A missense mutation of Gipc3 was previously reported to cause age-related hearing loss in mice. Point mutations of human GIPC3 were found in two small families, but association with hearing loss was not statistically significant. Here, we describe one frameshift and six missense mutations in GIPC3 cosegregating with DFNB72 hearing loss in six large families that support statistically significant evidence for genetic linkage. However, GIPC3 is not the only nonsyndromic hearing impairment gene in this region; no GIPC3 mutations were found in a family cosegregating hearing loss with markers of chromosome 19p. Haplotype analysis excluded GIPC3 from the obligate linkage interval in this family and defined a novel locus spanning 4.08 Mb and 104 genes. This closely linked but distinct nonsyndromic hearing loss locus was designated DFNB81.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Atteeq U
authors.initials: AU
authors.lastname: Rehman
authors.forename: Khitab
authors.initials: K
authors.lastname: Gul
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
authors.forename: Kwanghyuk
authors.initials: K
authors.lastname: Lee
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Rana A
authors.initials: RA
authors.lastname: Ali
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shahzad
authors.forename: Ateeq-Ul
authors.initials: AU
authors.lastname: Jaleel
authors.forename: Paula B
authors.initials: PB
authors.lastname: Andrade
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive / Q000235:genetics; D008040:Genetic Linkage; D056426:Genetic Loci; D006239:Haplotypes; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C452600:GIPC3 protein, human