Targeted gene/phenotype/disorder under study:

CLCN3 (OMIM 600580)


CLCN3  has recently been associated with neurodevelopmental disorder with hypotonia and brain abnormalities. Currently, there are only two publications describing CLCN3-associated disease (PMID: 34186028; PMID: 36536096). Most of the described patients have heterozygous de novo gain-of-function variants causing dominant disorder, and only one family had homozygous loss-of-function variant responsible for more severe recessive disease. We recently identified a patient with homozygous CLCN3 missense variant with a phenotype compatible with previously reported patients. In this project, we are looking for other patients with mono- and bi-allelic CLCN3 variants, to collect clinical and genetic data and further delineate the full clinical spectrum of this recently described disorder. The functional testing of human CLCN3 variants are on transfected cells, so there is no need for human samples.

Coordinating clinicians

Dr. Tinatin Tkemaladze –
Dr. Allan Bayat –
Dr. Reza Maroofian – 
Dr. Thomas Jentsch –


Department of Genetics, Tbilisi State Medical University, Tbilisi, Georgia
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London, UK
NeuroCure Centre of Excellence, Charité Universitätsmedizin Berlin, Berlin, Germany

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: No

2- Resampling of patients: No 

3- Linked to a translational/basic research project: Yes