Hearing impairment (HI) is the most common sensory defect in humans. About 1 child in 650 suffers from HI before speech acquisition. This prelingual deafness has a genetic cause in 60% of the cases and 70% of the cases with genetic cause are isolated or non-syndromic. In nearly all of these cases, the disorder is monogenic with more tendency to follow an autosomal recessive inheritance pattern (DFNB, 80% of the cases). Autosomal recessive prelingual deafness is known to be genetically highly heterogeneous.
Medlej-Hashim et al. (2002) described four members of a consanguineous Jordanian family with non-syndromic recessive deafness (NSRD). The disease manifested its symptoms in early childhood with a severe and bilateral hearing loss. Molecular analysis did not reveal any linkage to the DFNB1 locus. The family was subsequently subjected to a genome-wide linkage analysis, followed by homozygosity mapping, in order to determine the implicated NSRD locus. Medlej-Hashim et al. (2002) mapped the deafness locus in this family, designated DFNB33, to a 6.3-cM region on the telomeric side of chromosome 9 (9q34.3) between the microsatellite polymorphic markers D9S1826 and D9S1838 with a multipoint lodscore of 3.9. One candidate gene in the interval, coding for the chloride intracellular channel 3, CLIC3, was tested and excluded. Medlej-Hashim et al. (2002) concluded that the identification of a new NSRD locus, DFNB33, in this Jordanian family, adds to the wide genetic heterogeneity that characterizes hearing impairment and the genetic diversity in Middle-Eastern populations.
Belguith et al. (2009) studied the Jordanian family reported by Medlej-Hashim et al. (2002) and could not detect any mutations in 23 candidate genes in the interval on chromosome 9q34. Sequencing of these 23 candidate genes only showed 11 single nucleotide polymorphisms (SNPs) in the heterozygous state in affected individuals of this family. These results led Belguith et al. (2009) to rule out this locus as the true disease-related region. In a reanalysis of the genome-wide screening results from this family, Belguith et al. (2009) identified a second candidate peak on chromosome 10. Using additional markers to analyze this family, they identified linkage to a 13.8-cM region on chromosome 10p11.23-q21.1 (maximum lod score of 3.99 at D10S199 and D10S220). Belguith et al. (2009) reassigned the DFNB33 locus to chromosome 10p11.23-q21.1 and concluded that the previous assignment to 9q34.3 was not due to identity by descent, but rather due to homozygosity by chance. Sequence analysis excluded mutations in the CX40.1 and FXYD4 genes on chromosome 10.