Intellectual disability syndromic and non-syndromic
Gene: CAPZA2

CAPZA2 (capping actin protein of muscle Z-line alpha subunit 2)
EnsemblGeneIds (GRCh38): ENSG00000198898
EnsemblGeneIds (GRCh37): ENSG00000198898
OMIM: 601571, Gene2Phenotype
CAPZA2 is in 2 panels

2 reviews

Chris Ciotta (Victorian Clinical Genetics Services)

Green List (high evidence)

Now 4 unrelated families in the literature, Huang et al. (2020) identified two de novo missense variants, Pi (2022) in a letter to the editor identified a de novo in-frame del of Arg260 in an individual with seizures, hypotonia and developmental delay. Zhang et al. (2024) most recently identified a de novo canonical splice variant shown by RT-PCR to create exon skipping and an NMD-predicted frameshift. This individual presented with seizures and was later diagnosed with intellectual disability and mild motor delay.

All 4 individuals had seizures, 3/4 had speech delay and motor delay, 1/4 had microcephaly.

Disease mechanism not established, Loss of function and DN has been suggested. LoF variants in gnomad with over 1 het have poor quality and gene has a pLI score of 0.98.
Created: 8 Dec 2024, 11:59 p.m. | Last Modified: 8 Dec 2024, 11:59 p.m.

Panel Version: 1.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related

Publications

32338762, 38374166, 35856264

Created: 8 Dec 2024, 11:59 p.m.
Last Modified: 8 Dec 2024, 11:59 p.m.
Panel version: 1.19

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Created: 2 Jul 2020, 10:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability

Publications

32338762

Created: 2 Jul 2020, 10:21 p.m.

Panel version: 0.2726

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Literature

Phenotypes

Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related

OMIM

601571

Clinvar variants

Variants in CAPZA2

Penetrance

None

Publications

Panels with this gene