Between 1/2000 (0.05%) and 1/1000 (0.1%) of children are born with profound hearing loss.More than 50% of prelingual deafness is genetic, most often autosomal recessive and non-syndromic. This SALSA MLPA probemix can be used to detect several point mutations and most copy number changes in several genes resulting in hearing loss.
Defects in the GJB2 gene or the nearby GJB6 gene (13q12) account for 50% of autosomal recessive non-syndromic hearing loss in many populations and result in DFNB1 (Deafness, Neurosensory, autosomal recessive 1). In a large fraction (10-40%) of patients, only one mutant allele is identified. The carrier rate in the general population for a recessive deafness-causing GJB2 mutation is about one in 33. Defects of the GJB3 gene (1p35.1) encoding connexin 31, can cause early-onset bilateral non-syndromic sensorineural hearing loss, as well as the skin disorder erythrokeratodermia.
Both defects of the POU3F4 gene on chromosome Xq21.1 and microdeletions upstream of this gene have been identified in patients with X-linked deafness. Finally, Wolfram syndrome, whose highly variable clinical phenotype also includes hearing impairment as well as possible insulin-dependent diabetes mellitus and bilateral progressive optic atrophy, is caused by defects of the WFS1 gene (4p16.1) encoding the Wolframin protein.
The P163 probemix contains probes for all GJB2 and GJB6 exons, while four GJB3 probes are present. Two MLPA probes are included for the POU3F4 gene, as well as 6 probes targeting the conserved regions up to 1 Mb upstream of POU3F4. Also, probes have been included for each of the 8 WFS1 exons. In addition, several probes for the 13q11-q12 region are included. Finally, wild-type specific probes are present that will show a reduced probe signal when the 313del14, 101T>C, 235delC or 167delT mutation is present in the sample. The frequent GJB6 309 kb deletion will result in a reduced signal of four probes.