Prepair 1000+

Gene: MCOLN1

Green List (high evidence)

The MCOLN1 gene is associated with both AD & AR conditions (OMIM).

For carrier screening testing, the only relevant condition is AR Mucolipidosis IV MIM#252650.

Mucolipidosis IV is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by intellectual disability and ophthalmologic abnormalities. Onset is typically present by the end of the first year OMIM).

There are two common Ashkenazi Jewish founder variants, which account for 95% of all MLIV cases in Ashkenazi Jewish ancestry. The most common mutation (major AJ variant) is a splice site c.406-2A>G substitution and introduces a premature termination of the ML-1 translation. The other common mutation is a large gene deletion c.-1015_789del
called minor AJ variant (PMID: 32604955).

The genotype–phenotype correlation was proposed based on the location of the variants within the MCOLN1 gene (PMID: 32604955):
- Variants in the loop between the first and second transmembrane domain resulted in a mild phenotyp. Exception is the c.694A>C p.Thr232Pro variant that is associated with severe presentation.
- In patients with variants in the third transmembrane domain, mild neurological manifestation with progressive
retinal diseases was noted.
- The mildest MLIV phenotype results from variants in the fourth transmembrane domain.
- While mutations located between the fifth and sixth transmembrane domain were identified in patients with severe manifestation.

Created: 14 Jan 2025, 4:30 a.m. | Last Modified: 14 Jan 2025, 4:30 a.m.

Panel Version: 1.992

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mucolipidosis IV MIM#252650

Publications

• 33963976
• 32604955