A Novel ESRRB Deletion Is a Rare Cause of Autosomal Recessive Nonsyndromic Hearing Impairment among Pakistani Families

الملخص EN

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.