Hearing lossGene: SLC12A2
Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least 10 unrelated cases (and animal models) presenting significant sensorineural hearing loss, associated with variants in SLC12A2.
Created: 8 Sep 2020, 10:39 a.m. | Last Modified: 8 Sep 2020, 10:39 a.m.
Panel Version: 2.46
- PMID: 30740830 (2019) - Homozygous 22kb deletion identified in a 5-year-old male with GDD, sensorineural hearing loss, gastrointestinal abnormalities, early postnatal respiratory distress, generalised hypotonia, and absent salivation. Neuropsychological testing demonstrated profound delays in all developmental areas, with skills ranging from 1 to 6 months. The deletion was the result of uniparental paternal isodisomy.
Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein levels compared to control. Knockout mouse model recapitulated phenotypic features such as deafness, abnormal neuronal growth and migration, gastrointestinal abnormalities, and absent salivation.
- PMID: 32294086 (2020) - Homozygous SLC12A2 variant identified in one family with segregating hearing loss, as well as in three sporadic cases with de novo variants. All affected individuals presented non-syndromic congenital, severe/profound hearing loss. Some in vitro functional data showing localisation of SLC12A2 in several cells types of the cochlea and decreased expression of mutant transcripts compared to control.
- PMID: 32754646 (2020) - Compound heterozygous variants (c.1431delT and c.2006-1G>A) were identified in two sibs. The proband, an 8-year-old girl, presented a severe neurodevelopmental disorder (including severe ID), hearing impairment, gastrointestinal problems, hypotonia, and absent tear fluid, saliva, and sweat. Phenotypic overlap was noted in an affected older sister, who died at 22 days of age.
- PMID: 32658972 (2020) - Six unrelated children, all with mild-severe ID/DD, associated with de novo variants in SLC12A2. Additional clinical features included bilateral sensorineural hearing loss (2/6), abnormalities on brain MRI (2/4), and cerebral palsy (2/6). In addition, authors also identified three individuals from two unrelated families with congenital non-syndromic sensorineural hearing loss, associated with homozygous SCL12A2 variants. Some functional data in Xenopus laevis oocytes, indicating a role of SLC12A2 in neurogenesis.
Created: 8 Sep 2020, 10:36 a.m. | Last Modified: 8 Sep 2020, 10:36 a.m.
Panel Version: 2.45
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bilateral sensorineural hearing loss; Intellectual disability; Secretory defects
Three families reported.
Created: 3 Jun 2020, 10:45 a.m. | Last Modified: 3 Jun 2020, 10:45 a.m.
Panel Version: 2.18
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Congenital, severe to profound hearing loss
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: SLC12A2 were changed from to Bilateral sensorineural hearing loss; Intellectual disability; Secretory defects
Publications for gene: SLC12A2 were set to
Mode of inheritance for gene: SLC12A2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: slc12a2 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: SLC12A2.
SLC12A2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Expert