Monogenic hearing loss

Gene: SPATA5

Added new-gene-name tag, new approved HGNC gene symbol for SPATA5 is AFG2A.

Created: 16 Oct 2023, 6:18 p.m. | Last Modified: 16 Oct 2023, 6:18 p.m.

Panel Version: 4.18

Green List (high evidence)

Comment on list classification: As per review, multiple published cases with congenital HL as well as ID and epileptic encephalopathy, progressive microcephaly where congenital HL may be initial presentation prior to onset of other problems.

Publication of a case where sibling of a typically affected patient has isolated SNHL (PMID: 28293831) and biallelic pathogenic variants

Created: 11 Jun 2018, 11:20 a.m.

Tanaka et al PMID: 26299366 identified "14 individuals [from 10 families] with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants" in SPATA5

Puussep et al PMID: 29343804 describes 5 further patients "with psychomotor developmental delay, microcephaly, epilepsy and hearing impairment, who were thought clinically to have a mitochondrial disease with subsequent whole-exome sequencing analysis detecting compound heterozygous variants in the SPATA5 gene"

Szczaluba et al PMID: 28293831 describes a family where a sibling has isolated sensorineural hearing loss and the same two pathogenic SPATA5 variants as her more typically affected sister.

In addition, typically affected individuals may present as congenital SNHL on newborn hearing screen prior to onset of seizures, microcephaly and intellectual disability.

Created: 11 Jun 2018, 11:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome 616577

Publications

• PMID: 26299366
• PMID: 29343804
• PMID: 28293831

Variants in this GENE are reported as part of current diagnostic practice