title: Homozygosity mapping identifies a novel GIPC3 mutation causing congenital nonsyndromic hearing loss in a Saudi family.
abstract: Hearing loss is one of the most common sensory disorders in humans and has a genetic cause in 50% of the cases. Our recent studies indicate that nonsyndromic hearing loss (NSHL) in the Saudi Arabian population is genetically heterogeneous and is not caused by mutations in GJB2 and GJB6, the most common genes for deafness in various populations worldwide. Identification of the causative gene/mutation in affected families is difficult due to extreme genetic heterogeneity and lack of phenotypic variability. We utilized an SNP array-based whole-genome homozygosity mapping approach in search of the causative gene, for the phenotype in a consanguineous Saudi family, with five affected individuals presenting severe to profound congenital NSHL. A single shared block of homozygosity was identified on chromosome 19p13.3 encompassing GIPC3, a recently identified hearing loss gene. Subsequently, a novel mutation c.122 C>A (p.T41K) in GIPC3 was found. This is the first report of GIPC3 mutation in a Saudi family. The presence of the GIPC3 mutations in only one of 100 Saudi families with congenital NSHL suggests that it appears to be a rare cause of familial or sporadic deafness in this population.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. kramzan@kfshrc.edu.sa
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
authors.forename: Rabab
authors.initials: R
authors.lastname: Allam
authors.forename: Amal
authors.initials: A
authors.lastname: Berhan
authors.forename: Gheid
authors.initials: G
authors.lastname: Abuharb
authors.forename: Khalid
authors.initials: K
authors.lastname: Taibah
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D018912:Arabs / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19; D000072259:Connexin 26; D017630:Connexins; D008040:Genetic Linkage; D034381:Hearing Loss / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017630:Connexins; C452600:GIPC3 protein, human; C000607042:GJB2 protein, human; D000072259:Connexin 26