Table 3 Novel non-syndromic and syndromic hearing impairment candidate genes.
From: Exome sequencing of families from Ghana reveals known and candidate hearing impairment genes
Gene | F-ID | Phenotype | Nucleotide change | Protein change | Rs-number | Inh | GT | Expression in the mouse inner ear | Previous/animal studies |
|---|---|---|---|---|---|---|---|---|---|
INPP4B | Fam2 | NSHI | c.1848G>C | p.(Q616H) | rs147919355 | AR | Het | Yes | Depletion of INPP4B suppresses callosal axon formation in the developing mice and may cause mild to severe cognitive impairment INPP4B regulates nerve conduction velocity Mouse models and rat models express the gene in the inner ear. |
c.1271T>C | p.(I424T) | rs747224392 | AR | Het | |||||
CCDC141 | Fam26 | NSHI | c.704A>G | p.(D235G) | rs1029313097 | AR | Het | Yes | CCDC141 variants have been implicated in Kallmann Syndrome, and though rare, HI is reported in some Kallmann Syndrome patients. Mouse models express the gene in the inner ear. Ccdc141-null mice showed impaired recognition memory and spatial reference memory. |
c.202G>A | p.(E68K) | rs540836199 | AR | Het | |||||
MYO19 | Fam40 | NSHI | c.949G>T | p.(A317S) | rs199866785 | AR | Hom | Yes | Mouse models express the gene in the inner ear. The ortholog of the gene was associated with autistic disorder in different animals such as Canis lupus familiaris, Pan paniscus, Sus scrofa, and Chinchilla lanigera. In humans, Myosin 19 functions as an actin-based motor for mitochondrial movement in vertebrate cells. |
Case1 | NSHI | c.1300G>A | p.(A434T) | rs375962449 | AR | Het | |||
c.2552C>T | p.(P851L) | rs749344013 | AR | Het | |||||
DNAH11 | Fam44 | NSHI | c.11232C>G | p.(I3744M) | rs201120788 | AR | Het | Yes | DNAH11 was implicated in primary ciliary dyskinesia and Kartagener syndrome which has HI as one of its symptoms. |
c.12969G>C | p.(Q4323H) | rs191802172 | AR | Het | |||||
Case2 | c.6118C>T | p.(R2040C) | rs199772877 | AR | Het | ||||
c.846G>A: | p.(M282I) | rs375023124 | AR | Het | |||||
Case3 | c.7295G>A | p.(R2432Q) | rs769003090 | AR | Het | ||||
c.6131G>A | p.(R2044Q) | rs372051486 | AR | Het | |||||
SOX9 | Fam45 | NSHI | c.432-3C>A | – | rs1033320617 | AD | Het | Yes | SOX9 is essential for cochlear development in mice. Mutant mice had a HI phenotype. Depletion of Sox9 resulted in defective vestibular structures, semi-circular canals, and utricle developments. |
PAX8 | Fam39 | Waardenburg syndrome | c.968C>G | p.(P323R) | rs1573435665 | AD | Het | Yes | (Pax8−/− mice did not respond to sound when examined by the auditory brain stem response (ABR) test. |
POTEI | Fam6 | NSHI | c.1676G>C | p.(G559A) | rs1254207451 | AR | Het | – | – |
c.409C>T | p.(R137X) | rs536831847 | AR | Het |
