A novel synonymous mutation causing complete skipping of exon 16 in the SLC26A4 gene in a Korean family with hearing loss.

[pendred syndrome]

Mutations in PDS (or SLC 26 A 4 ) cause both Pendred syndrome (PS ) and DFNB 4 , two autosomal recessive disorders that share hearing loss as a common feature . PS and DFNB 4 are genetically homogeneous disorders caused by bi -allelic SLC 26 A 4 mutations . Here , we report a novel synonymous mutation (c .1803 G >A , p .Lys 601 Lys ), that caused aberrant splicing in two Korean family members who were clinically considered to have DFNB 4 , along with congenital hearing loss and dilated vestibular aqueducts (DVA ).After extracting DNA from whole blood using standard procedures , the 21 exons and flanking introns of SLC 26 A 4 were amplified with PCR . To evaluate the implication of a novel synonymous mutation (c .1803 G >A ), we used The Berkeley Drosophila Genome Project (BDGP ) (http ://www .fruitfly .org /) as a splice site prediction program and performed exon trapping analysis .In molecular analysis of the 21 exons of SCL 26 A 4 , we detected a known splicing mutation (c .919 -2 A >G , heterozygote ) and a novel variant (c .1803 G >A , heterozygote ) in the patients (II -1 and II -2 ). According to in silico analysis , the novel variant (c .1803 G >A ) affects canonical splice donor nucleotide positioning . To define the transcript level effects of this novel 1803 G >A variant , we performed exon trapping and confirmed that exon 16 is completely skipped in this variant type .We report a novel synonymous mutation (c .1803 G >A ) causing complete exon 16 skipping in the SLC 26 A 4 gene in two Korean family members with hearing loss . This is the first case of a synonymous SNP (c .1803 G >A ) affecting vestibulocochlear organs through altering splicing accuracy by causing a complete skipping of exon 16 . An important issue raised by this study is that synonymous mutations that have been previously ignored in clinical diagnoses must now be considered as potential pathogenic mutations .

Diseases
Validation

Diseases presenting "congenital hearing loss" symptom

holt-oram syndrome

pendred syndrome

This symptom has already been validated