ClinGen Dosage Sensitivity Curation Page

CASZ1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
8263302 C Yuen RK et. al., (2017) The authors performed Whole Genome Sequencing (WGS) of 5,193 unique individuals from families with Autism Spectrum Disorder (ASD). A CASZ1 frameshift insertion variant was identified de novo in two probands with Autism Spectrum Disorder. The specific phenotype and parental information is not available. Functional studies were not performed.

Haploinsufficiency phenotype comments:

Overall CASZ1 may be considered a candidate gene potentially related with the phenotype although further evidence is required to clarify a possible link with disease. For the paper below: Qiu et al. (2017) (PMID:28099117) and Huang et al. (2017) (PMID:27693370), questions remain with regards to how the CASZ1 gene was selected for testing and also if there was any additional testing performed in the probands. It is not clear if these studies represent two single-gene sequencing or are part of the same study. Qiu et al. (2017) (PMID:28099117) Studied a Han Chinese cohort of 138 patients with idiopathic Dilated Cardiomyopathy (DCM) and 200 unrelated healthy individuals used as controls. The coding exons and flanking introns of the CASZ1 gene were sequenced. The p.K351X nonsense mutation was detected in an index patient with Dilated Cardiomyopathy (DCM) which was transmitted as an autosomal dominant trait and co-segregated with DCM in carrier family members over 2 generations with complete penetrance. The mutant residue at amino acid 351 was is absent in gnomAD and highly conserved evolutionarily. Reporter gene assay performed in human cell cultures demonstrated no transcriptional activity by the mutant protein compared to wild type. Huang et al. (2017) (PMID:27693370) Studied a Han Chinese cohort of 172 patients with Ventricular Septal Defects (VSD) and 200 unrelated healthy individuals used as controls. The coding exons and flanking introns of the CASZ1 gene were sequenced. The p.L38P missense mutation was detected in an index patient with VSD, which was transmitted as an autosomal dominant trait and co-segregated with VSD in carrier family members over 3 generations with complete penetrance. The mutant residue at amino acid 38 was absent in gnomAD and highly conserved evolutionarily and insilico studies predicted the variant to be damaging. Reporter gene assay performed in human cell cultures demonstrated reduced transcriptional activity with the mutant protein compared to wild type.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No duplications involving only the entire CASZ1 gene reported