Autosomal Dominant Nonsyndromic Hearing Loss Loci Characteristics Locus/Location Gene Name Onset/Decade Type DFNA1/5q31 HDIA1 Postlingual/1st-2nd Progressive DFNA2/1p34 GJB3(Cx31) Postlingual/2nd-3rd Progressive DFNA3/13q12 GJB2(Cx26) Prelingual Stable DFNA4/19q13 GJB2(Cx30) Postlingual/2nd Progressive DFNA5
Postlingual/1st-2nd Progressive DFNA6/4p16.
DFNA5 is one of the deafness genes that known to cause autosomal dominant NSHL.
DFNA5 is one of the deafness genes with currently unknown function, which was mapped to chromosome 7p15 in 1995 and identified in 1998 in an extended Dutch family.
For the detection of alternative splicing in other parts of the mRNA in DFNA5 , the primers were selected as previously described.
Following this step-by-step filtering protocol, only one novel DFNA5 splice site mutation, IVS8+1 delG, was likely to be pathogenic according to this criterion [Figure 3] and [Figure 4]a.
In the present study, we described the ninth DFNA5 family with autosomal dominant hearing impairment.
In this study, we cannot rule out the possibility that environmental factors modify the clinical phenotype of DFNA5 mutation, as the patient III-9 who suffered from chronic suppurative otitis media in the left ear clearly demonstrated a different severity of hearing loss for both ears, while the other seven patients without ear disease exhibited a symmetric hearing loss [Figure 2].
Until date, a total of six deafness-causing mutations in the DFNA5 gene have been reported in nine families [Table 2].
The molecular pathogenic mechanism of NSHL associated with DFNA5 mutations remains unclear.
In this family, a novel DFNA5 mutation IVS8+1 delG leading to skipping of exon 8 was identified through targeted gnomic sequencing and co-segregation analysis.