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Updated: Jul 16, 2026
07:45
An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
Published on: October 21, 2014
Claudin-11-Mediated Hypomyelinating Leukodystrophy 22: New Insights Into Pathogenic Mechanisms
Fabio Acquaviva1, Serena Troisi2, Gabriella Errichiello3
1Medical Genetics Unit, Department of General and Emergency Pediatrics, AORN Santobono-Pausilipon, Naples, Italy.
Clinical Genetics
|July 14, 2026
Summary
A novel homozygous CLDN11 gene variant causes a rare leukodystrophy, expanding the genetic understanding of this condition and suggesting distinct disease mechanisms. This finding has implications for diagnosis and genetic counseling.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Claudin-11 (CLDN11) gene variants have been linked to hypomyelinating leukodystrophy.
- Previous reports identified de novo dominant stop-loss variants in CLDN11-related disorders.
Purpose of the Study:
- To investigate a novel homozygous CLDN11 variant to broaden the genetic and clinical spectrum of the disease.
- To elucidate the pathogenic mechanism and inheritance pattern of CLDN11-related leukodystrophy.
Main Methods:
- Comprehensive clinical, neuroradiological, and genetic evaluation of a pediatric patient.
- Brain MRI and MR spectroscopy for assessing myelination.
- Next-generation sequencing with parental segregation analysis to identify and confirm the variant.
Main Results:
- A novel homozygous CLDN11 start-loss variant (c.1A>G; p.Met1Val) was identified, predicted to cause biallelic loss of function.
- The patient presented with global developmental delay, hypotonia, esotropia, and cognitive impairment, with diffuse supratentorial hypomyelination.
- Parents were heterozygous carriers, supporting an autosomal recessive inheritance pattern.
Conclusions:
- This case establishes an autosomal recessive inheritance for CLDN11-related leukodystrophy, distinct from previously reported dominant mechanisms.
- The identified variant expands the mutational spectrum of CLDN11 disorders.
- The findings suggest different pathogenic mechanisms and have implications for diagnosis and genetic counseling.
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