Retinal disorders

Gene: SLC38A8

Green List (high evidence)

Biallelic variants in SLC38A8 cause isolated foveal hypoplasia, chisamal misrouting in the absence of pigmentation defects. The variable phenotype being anterior segment dysgenesis (Poulter et al., 2013). Bare in mind chiasmal misrouting is not always reported due to lack of access to the visual evoked potentials (VEP) test, technical difficulty in performing the test on infants and inconsistent results during childhood (Campbell et al., 2019). The differential feature of SLC38A8 is the absence of pigmentation defects however assessing pigmentation status proves challenging especially in fair populations thus some genuine SLC38A8 cases are misdiagnosed as albinism (Campbell et al., 2019). Oculomotor defects such as nystagmus accompanies isolated foveal hypoplasia.

Created: 7 Mar 2022, 6:49 p.m. | Last Modified: 2 Jul 2024, 5:57 p.m.

Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
foveal hypoplasia, chiasmal misrouting, anterior segment dysgenesis; nystagmus

Publications

• Poulter et al (2013) (PMID: 24290379)
• Campbell et al. (2019) (DOI: 31719542)

Green review from Mohammed Derar on green gene so no change in rating needed. Phenotypes updated.

Created: 25 May 2022, 1:18 p.m. | Last Modified: 25 May 2022, 1:18 p.m.

Panel Version: 2.272

PMID: 32744312 Kuht et al 2020 - used a custom-targeted next generation sequencing gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. They report 16 novel SLC38A8 mutations in 11 subjects from nine families. 2 families had homozygous variants, the other 7 had compound het variants. There was a mixture of missense, splice variants and nonsense variants. 90% of cases were initially misdiagnosed, prior to NGS, as PAX6-related phenotype or ocular albinism. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening.

Created: 2 Dec 2020, 3:21 p.m. | Last Modified: 2 Dec 2020, 3:21 p.m.

Panel Version: 2.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218; foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216

Publications

• 32744312

Green List (high evidence)

Comment on list classification: Updated rating from Grey to Green after review and advice from Chris Campbell: Gene was added and rated Green by Mervyn Thomas. >3 unrelated cases of SLC38A8 variants causing foveal hypoplasia (MIM:609218) which is relevant phenotype for panel.

Created: 21 Sep 2017, 7:54 a.m.

Comment on mode of inheritance: Biallelic mode of inheritance supported by OMIM.

Created: 21 Sep 2017, 7:52 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Foveal hypoplasia 2 with optic nerve misrouting with or without anterior segment dysgenesis

Publications

• PMID:1546
• 6012, 2429
• 0379, 2404
• 5842

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

Green List (high evidence)

Associated with foveal hypoplasia. OMIM #609218

Created: 28 Nov 2016, 8:50 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis

Publications

• 24290379
• 24045842