Retinal disorders

Gene: MCOLN1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:45 p.m. | Last Modified: 2 May 2024, 1:45 p.m.

Panel Version: 5.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence for this gene to be added with a green rating in this panel as patients with MCOLN1-associated mucolipidosis IV present with a limited ocular phenotype including retinal dystrophy.

Created: 28 Jul 2023, 5:58 a.m. | Last Modified: 28 Jul 2023, 5:58 a.m.

Panel Version: 4.17

Mucolipidosis type IV caused by biallelic variants in MCOLN1 gene ism a lysosomal disease that primarily affects the central nervous system. It manifests with severely impaired psychomotor development, and later onset, gradual neurological decline paralleled by cerebellar degeneration and neuroaxonal injury. In addition, they also manifest retinal dystrophy, which develops in the first years of life and rapidly progresses in adolescence, leaving patients legally blind by the second decade (PMID:33965501).

The following are some of the reported cases:
PMID:17239335 - Compound heterozygous variants in MCOLN1 were identified in a patient with mucolipidosis type IV (ML IV), who had low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years.
PMID:25156245 - An Italian child with ML IV was identified with homozygous MCOLN1 variants (c.395_397delCTG & c.468_474dupTTGGACC), while his parents were heterozygous for the same variants. Ophthalmological manifestations included esotropia, bilateral corneal clouding and severe myopia.
PMID:35205297 - Six patients from two Omani families with ML IV were identified with a novel variant (c.237+5G>A) in MCOLN1 gene, which is not present in control subjects screened with a high-resolution melting (HRM) assay. The patients displayed ophthalmic manifestations including corneal haziness, pigmentary retinopathy and ERG-rod cone dysfunction.

This gene has also been associated with relevant phenotypes both in OMIM (MIM #252650) and DD and eye panels of Gene2Phenotype (with 'definitive' rating). The ophthalmological manifestations including corneal clouding, progressive retinal degeneration and optic atrophy has been reported as part of the OMIM phenotype.

Created: 28 Jul 2023, 5:54 a.m. | Last Modified: 28 Jul 2023, 6:08 a.m.

Panel Version: 4.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mucolipidosis IV, OMIM:252650

Publications

• 17239335
• 25156245
• 33965501
• 35205297

Green List (high evidence)

Retinal degeneration is a known feature of MCOLN1-associated mucolipidosis IV, and there are reports of patients presenting with a limited ocular phenotype including retinal dystrophy
Sources: Literature

Created: 3 Jul 2023, 4:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 17239335
• 1488220
• 18326692

Mode of pathogenicity
Other