White matter disorders and cerebral calcification - narrow panel

Gene: CLDN5

Green List (high evidence)

This gene currently has no phenotype in OMIM but the paper PMID:36477332 mentions the same gene name so adding the gene-checked tag.

Created: 16 Oct 2023, 4:41 p.m. | Last Modified: 16 Oct 2023, 4:41 p.m.

Panel Version: 3.20

The rating of this gene has been updated to green and the mode of inheritance set to "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 10:40 a.m. | Last Modified: 11 Oct 2023, 10:40 a.m.

Panel Version: 3.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.

Created: 1 Jun 2023, 8:42 a.m. | Last Modified: 1 Jun 2023, 8:42 a.m.

Panel Version: 3.14

PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All patients except one (patient 2 who had a single MRI taken at 4 days of age) showed pontine atrophy and brain calcifications from neuroimaging.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature

Created: 31 May 2023, 4:01 p.m. | Last Modified: 1 Jun 2023, 8:42 a.m.

Panel Version: 3.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Brain calcifications

Publications

• 36477332