White matter disorders and cerebral calcification - narrow panel

Gene: CLDN11

Green List (high evidence)

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

Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.9

Not associated with relevant phenotype in OMIM (entry last edited on 01/14/2013) or Gen2Phen. Two stop loss variants reported in three unrelated cases. Both variants resulted in an 39aa extension - c.622T>C, p.(208Glnext*39) in two individuals and c.622T>G, p.(208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T>C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay (PMID 33313762). The reporting authors predict that the extended claudin-11 forms an alpha helix which is not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins.

Created: 20 Apr 2021, 1:43 p.m. | Last Modified: 20 Apr 2021, 1:47 p.m.

Panel Version: 1.39

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

Created: 20 Apr 2021, 1:32 p.m. | Last Modified: 20 Apr 2021, 1:32 p.m.

Panel Version: 1.39

Green List (high evidence)

In three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia, 2 different heterozygous de novo stop-loss variants were identified. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.
Sources: Literature

Created: 19 Apr 2021, 8:38 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypomyelinating leukodystrophy

Publications

• 33313762

Variants in this GENE are reported as part of current diagnostic practice