Recurrent episodic apnoea

Gene: SLC6A5

Green List (high evidence)

The rating of this gene has been set to Green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 2:43 p.m. | Last Modified: 1 Feb 2023, 2:43 p.m.

Panel Version: 0.91

Green List (high evidence)

Comment on classification of gene: This gene should be rated GREEN as this gene has been associated with apnoea from >3 unrelated cases.

SLC6A5 has been associated with hyperekplexia in both OMIM and G2P. It is reported with both autosomal dominant (AD) and autosomal recessive (AR) inheritance in OMIM, although AD was reported only in one patient. However, only hyperekplexia caused by AR was reported in G2P. Apnoea was associated as a clinical phenotype in both resources.

PMID:31604777 reports an infantile case of episodic apnoea, which displayed compound heterozygous variants (c.1430delC (p.Ser477PhefsTer9)/ c.1429T > C (p.Ser477Pro)). Similarly, 3 of 16 patients with hyperekplexia from PMID:27843043 were identified with autosomal recessive variants in SLC6A5 gene and had tonic-apneic spells. In addition, PMID:24030948 reports that ~80% of cases (14 out of 18) with SLC6A5 variants had recurrent apnoea attacks.

As all cases except the one mentioned in OMIM was reported with AR inheritance, I have chosen BIALLELIC inheritance.

Created: 3 Jan 2023, 2:40 p.m. | Last Modified: 3 Jan 2023, 2:43 p.m.

Panel Version: 0.65

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperekplexia 3, OMIM:614618

Publications

• 24030948
• 27843043
• 31604777

Gene added on recommendation of Dr Emma Matthews.

Created: 21 Dec 2022, 2:49 p.m. | Last Modified: 21 Dec 2022, 2:49 p.m.

Panel Version: 0.2