Vahava et al. (1998) studied progressive hearing loss in an Israeli Jewish family that traced its ancestry to Italy and to subsequent migrations through various North African and Middle Eastern countries, including Tunisia, Libya, and Egypt, with branches ... Vahava et al. (1998) studied progressive hearing loss in an Israeli Jewish family that traced its ancestry to Italy and to subsequent migrations through various North African and Middle Eastern countries, including Tunisia, Libya, and Egypt, with branches of the family now living in Israel, the United States, and Belgium. Five generations demonstrated autosomal dominant inheritance of progressive deafness. Earliest record of a hearing-impaired family member concerned an individual born in 1843 in Libya. He had 4 children, only 1 of whom was affected. Hearing loss in this kindred, referred to as family H, began between ages 18 and 30, with a moderate to severe defect in hearing by age 50. Collin et al. (2008) reported a large Dutch family in which multiple members had hearing loss. The was large clinical variability in terms of age at onset, levels of progression, and shape of audiograms. For example, 1 patient reported subjective onset around puberty, whereas another had onset at 20 years of age.
In searching for candidate genes in the DFNA15-linked region, Vahava et al. (1998) noted that the POU domain, class 4, transcription factor 3 gene (POU4F3) may lie on 5q, on the basis of the localization of mouse Pou4f3 ... In searching for candidate genes in the DFNA15-linked region, Vahava et al. (1998) noted that the POU domain, class 4, transcription factor 3 gene (POU4F3) may lie on 5q, on the basis of the localization of mouse Pou4f3 and the homology of human chromosomes 5 and 18 with mouse chromosome 18. POU4F3 was considered an excellent candidate for a gene causing human deafness because targeted deletion of both alleles of Pou4f3 caused complete deafness in mice. To map POU4F3 more precisely, they synthesized primers for the human POU4F3 cDNA sequence and used these to amplify pools of the CEPH3 yeast artificial chromosome (YAC) library. In this way, YACs containing markers linked to deafness in family H were found, indicating that POU4F3 must lie within the DFNA15-linked region. Using primers designed to amplify and sequence the entire coding region, they found an 8-bp deletion (602460.0001) in exon 2 of the POU4F3 gene. The predicted result of this deletion was a frameshift beginning at codon 295 and a premature translation stop at position 299. Deletion was not found in the POU4F3 gene of 114 unrelated individuals of various North African and Middle Eastern Jewish ancestry selected to represent the contribution of various ethnic Jewish populations to family H. In affected members of 2 unrelated Dutch families with autosomal dominant hearing loss, Collin et al. (2008) identified 2 different heterozygous mutations in the POU4F3 gene (602460.0002 and 602460.0003, respectively).