title: A Novel ESRRB Deletion Is a Rare Cause of Autosomal Recessive Nonsyndromic Hearing Impairment among Pakistani Families.
abstract: Mutations in the estrogen-related receptor beta (ESRRB) gene is the underlying cause of autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to the DFNB35 locus which maps to 14q24.3. A genome scan of a large consanguineous Pakistani pedigree with ARNSHI established linkage with a maximum multipoint LOD score of 4.2 to the 14q24 region and the region of homozygosity contained the ESRRB gene. Sequencing of the ESRRB gene using DNA samples from hearing-impaired family members uncovered a novel three-nucleotide deletion c.1018_1020delGAG (p.Glu340del). The deletion segregates with hearing impairment in the pedigree and was not observed in 500 control chromosomes. The deletion of glutamic acid residue occurs in the ligand-binding domain of ESRRB protein. It is expected that the deletion affects the ligand-binding activity of the domain in ESRRB, which leads to the ARNSHI.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Tx 77030, USA.
authors.forename: Kwanghyuk
authors.initials: K
authors.lastname: Lee
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Regie Lyn P
authors.initials: RL
authors.lastname: Santos-Cortez
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal