Monogenic hearing loss

Gene: SLC26A5

Comment on list classification: Changing rating from red to green as 3 unrelated cases now reported.

Created: 17 Feb 2019, 10:45 p.m.

Provisionally associated with ?Deafness, autosomal recessive 61 (613865) in OMIM.

PMID: 24164807 - Mutai et al (2013) - 2 siblings with hearing loss had compound heterozygous SLC26A5 with c.209G >A (p.W70X) and c.390A >C (p.R130S) mutations. Parents with normal hearing each carry one variant.

PMID: 26824437 - Matsuanga and Morimoto (2016) - abstract only accessed, but same variants in two siblings as reported in Mutai et al. so possibly same family.

PMID: 26969326- Sloan-Heggen et al (2016) - 1 patient with sporadic congenital Autosomal recessive non-syndromic hearing loss found to be heterozygous for 2 missense variants: NM_001167962:c.355C>T, p.Pro119Ser and NM_001167962:c.298G>A, p.Ala100Thr.

3rd case reported by GOSH

Created: 17 Feb 2019, 10:43 p.m.

Green List (high evidence)

(Homozygous splice acceptor mutation -2A>G, 1 family, both parents confirmed carriers in our lab): Mutai et al (2013) PMID 24164807 - two sibs compound het nonsense and missense, parents normal hearing each carry one variant. Matsuanga and Morimoto (2016) PMID 26824437 report siblings of same gender with same genotype ? re-report of same family. Sloan-Heggen et al (2016) PMID 26969326 report one patient compound het for two missense variants patient reported to have sporadic congenital onset HL.

Created: 17 Feb 2019, 5:50 p.m.

Publications

• 24164807
• 6824437
• 26969326

Comment on list classification: PMID: 12719379 reports variant IVS2-2A>G with an association for recessive non-syndromic deafness in two unrelated families. PMID: 16086836 reports that this variant is not found in significantly more subjects than controls. PMID: 19492055 did not find an association between novel variants and hearing loss. PMID: 24164807 reports the gene as a candidate gene for hearing loss, reporting compound heterozygous mutations in 2 Japanese sisters. PMID: 25262649 a reported pathogenic variant was found at a high allele frequency in controls. They suggest that attention should be paid towards this genes as variants reported to cause non-syndromic hearing loss are questionable. Overall conclusion - not enough evidence for this gene to be included on the green list.

Created: 22 Feb 2016, 6:07 p.m.

I don't know

Mouse models are convincing. Few human variants have been reported.

Created: 24 Feb 2016, 11:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#613865:?Deafness, autosomal recessive 61[Hearing loss, bilateral, moderate-to-profound]

I don't know

Biologically very plausible but very few convincing mutations reported.

Created: 13 Oct 2015, 7:50 p.m.

Publications

• PMC4185121