Lysosomal Storage Disorder

Gene: VPS33A

Green List (high evidence)

Now two missense variants reported with disease in at least 15 probands/families
PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells.
PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family
PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family
PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts

Created: 9 Oct 2022, 6:32 a.m. | Last Modified: 9 Oct 2022, 6:32 a.m.

Panel Version: 1.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012

Publications

• 28013294
• 27547915
• 31936524
• 36153662

I don't know

Single variant (R498W) reported in the Turkish and Yakut population. Functional studies support association of this gene to lysosomal dysfunction. Amber pending additional reports.

Not in any of PanelApp UK's list.

Created: 22 Jul 2020, 5:53 a.m. | Last Modified: 22 Jul 2020, 5:53 a.m.

Panel Version: 0.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mucopolysaccharidosis-plus syndrome (MIM#617303)

Publications

• 28013294
• 27547915