Paediatric or syndromic cardiomyopathy

Gene: CASZ1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:01 p.m. | Last Modified: 26 Sep 2024, 3:01 p.m.

Panel Version: 5.12

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: As reviewed by Ludmila Volozonoka, there is sufficient evidence available (three unrelated cases and some functional studies) for the promotion of this gene to green rating in the next GMS update.

Created: 17 Apr 2024, 10:28 p.m. | Last Modified: 17 Apr 2024, 10:28 p.m.

Panel Version: 3.46

PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.

Created: 17 Apr 2024, 10:21 p.m. | Last Modified: 17 Apr 2024, 10:26 p.m.

Panel Version: 3.44

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
dilated cardiomyopathy, MONDO:0005021; left ventricular noncompaction, MONDO:0018901

Publications

• 28099117
• 31268246
• 36293425

Green List (high evidence)

Loss of Function variants described in patients with pediatric dilated cardiomyopathy, pediatric LVNC (36293425; 31268246). Our laboratory identified the LOF variant in a pediatric patient with LVNC.

The limited implication in congenital ventricular septal defect (27693370) - authors identified a missense variant.

Review article on CASZ1 (37509718).
Sources: Literature

Created: 6 Feb 2024, 10:34 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pediatric Dilated Cardiomyopathy; Pediatric LVNC

Publications

• 36293425
• 31268246
• 28099117
• 27693370
• 37509718