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Gene: ALG2

I don't know

HGNC approved symbol/name: ALG2
Phenotype(s) are severe and age of onset <18 years old

Association with CMS:
Two families reported (PMID 24461433 and 23404334), same variant identified in both families, likely founder variant.
Proband with pronounced truncal hypotonia, proximal muscle weakness and feeding difficulties at birth (PMID 34980536)

Association with CDG:
One individual with CDG, compound heterozygous, presented in 1st year of life with intellectual disability, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities (PMID: 12684507)
3 probands (including a sibling pair) from 2 families from the same region affected with CDG (PMID: 33644825 and 30397276), presenting with severe neurological and neuro-developmental disorders. This paper cites up to nine ALG2-CDG patients have been reported worldwide.

Model to explore effect of ALG2 gene variants on embryonic development showed abnormalities in embryos with ALG2 variants, and phenotype rescue with injection of mRNA (PMID: 34106226)

Created: 22 Aug 2024, 6:51 a.m. | Last Modified: 22 Aug 2024, 6:51 a.m.

Panel Version: 1.236

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ii, MIM# 607906; Myasthenic syndrome, congenital, 14, MIM# 616228

Publications

• 33644825
• 23404334
• 24461433
• 12684507
• 30397276
• 34980536
• 34106226

Red List (low evidence)

Insufficient evidence for gene-disease association to be included in a screening panel.

Created: 22 Jun 2022, 2:39 a.m. | Last Modified: 22 Jun 2022, 2:39 a.m.

Panel Version: 0.1

I don't know

One additional variant reported in association with CDG on top of the previously reviewed patients reported with CDG/congenital myasthenia

PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276)

Created: 11 Jul 2022, 7:05 a.m. | Last Modified: 11 Jul 2022, 7:05 a.m.

Panel Version: 0.31

Amber in Mendeliome. For removal from this gene list.

Association with myasthenia: Two families reported, same, likely founder variant.

Association with CDG: one individual with multisystemic disorder with ID, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities reported in PMID 12684507. Fibroblasts showed severely reduced enzymatic activity.

Created: 7 Jun 2022, 11:36 p.m. | Last Modified: 7 Jun 2022, 11:36 p.m.

Panel Version: 0.0

Phenotypes
Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906

Publications

• 23404334
• 24461433
• 12684507