Ciliopathies

Gene: ZNF423

Deshpande et al. 2020 (PMID: 32925911) produced Zfp423-mutant mice harbouring various variants, including the p.P913L and p.P506fsX43 patient variants. Notably, p.P913L did not result in any abnormalities in brain structures or gait, while mice homozygous for p.H1277Y displayed features such as gross ataxia, vermis agenesis, reduced cortical thickness, and incomplete corpus callosum.

Tang et al., 2022 (PMID: 33323469) identified a Chinese patient with a homozygous p.H353Q variant in the ZNF423 gene for which both parents were heterozygous carriers. The phenotype was consistent with Joubert syndrome including nephronophthisis, developmental delay and cerebellar vermis hypoplasia.

Created: 31 Mar 2022, 2:27 p.m. | Last Modified: 31 Mar 2022, 2:27 p.m.

Panel Version: 1.27

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844

Publications

• 22863007
• 32925911
• 33323469

I don't know

Limited reports, single publication in 2012 reported AD and AR inheritance. Mechanism not well established. Pending additional reports.

2 Turkish sibs with Joubert syndrome with homozygous mutation in the ZNF423 gene.
Two additional patients with Joubert syndrome were found to carry heterozygous ZNF423 mutations , which caused a dominant-negative effect on protein function in cellular studies. Published variants not present in gnomAD at unexpected frequencies and minimal LoF variants in gnomAD

Created: 20 May 2020, 3:45 a.m. | Last Modified: 20 May 2020, 3:45 a.m.

Panel Version: 0.162

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 19 (MIM#614844)

Publications

• 22863007

Mode of pathogenicity
Other

Red List (low evidence)

2 Turkish sibs with Joubert syndrome with homozygous mutation in the ZNF423 gene.
Two additional patients with Joubert syndrome were found to carry heterozygous ZNF423 mutations , which caused a dominant-negative effect on protein function in cellular studies.

Created: 3 Jan 2020, 5:44 a.m. | Last Modified: 3 Jan 2020, 5:44 a.m.

Panel Version: 0.14

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 19, OMIM# 614844

Publications

• 22863007