CLDN11 is located at 3q26.2. It encodes claudin-11, a member of the claudin tight junction family. Claudin-11 has a critical structural role in the radial component of the myelin sheath.
Riedhammer et al. (2021) identified two de novo heterozygous variants in CLDN11 (NM_005602.5) in 3 unrelated children with hypomyelinating leukodystrophy (HLD22):
• c.622T>C, p.(*208Glnext*39) in two individuals
• c.622T>G, p.(*208Gluext*39) in one individual
Both variants are at the same nucleotide, and both result in a stop-loss which is predicted to extend the protein by 39 residues. The variants were found by exome sequencing and confirmed by Sanger sequencing. They were absent from public databases, including gnomAD. Evidence that the mutant transcript does not lead to nonsense-mediated mRNA decay, came from fibroblast studies in one patient, which showed CLDN11 transcript levels similar to those of controls. Molecular models show that the added residues add an alpha-helix domain to the cytoplasmic tail of the protein. It is predicted that this prevents its incorporation into the cell membrane and thus affects protein-protein interactions.
CLDN11