Incidentalome

Gene: GLA

Green List (high evidence)

- Variants causing the additional cardiac phenotype are enriched in exon 6 (OMIM)
- Females can be affected but with variable severity unexplained by skewed X-inactivation (PMID: 31613176). May be due to DN mechanism

LOF and DN mechanism:
- Many NMD PTCs reported (Decipher) but truncating variant (last exon) shows loss of enzyme activity when co-expressed with wildtype (PMID: 8878432). This paper also show variably truncated variants with increased enzyme activity, however no recent papers describe/support this mechanism.
- Missense variants show undetectable protein and when coexpressed with wildtype protein maintains enzyme activity loss (PMID: 31613176)

Created: 15 Oct 2020, 11:31 p.m. | Last Modified: 15 Oct 2020, 11:31 p.m.

Panel Version: 0.43

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Fabry disease 301500; Fabry disease, cardiac variant 301500

Publications

• PMID: 8878432
• 31613176

Mode of pathogenicity
Other

Green List (high evidence)

HCM can be a presenting feature of Fabry.

Created: 29 Jul 2020, 6:50 a.m. | Last Modified: 5 Aug 2020, 6:59 a.m.

Panel Version: 0.146

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Fabry disease (MIM# 301500)

Red List (low evidence)

PMID: 30681346
- curated as a syndromic gene by ClinGen hypertrophic cardiomyopathy (HCM) working group

DEFINITIVE in clingen for Fabry disease.
No evidence of association with isolated HCM

Created: 29 Jul 2020, 4:44 a.m. | Last Modified: 29 Jul 2020, 4:44 a.m.

Panel Version: 0.89

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Fabry disease (MIM# 301500)

Publications

• 30681346