Targeted gene under study:
ELOVL1 (OMIM 611813)
Abstract
ELOVL1 has recently been associated with neurodevelopmental disorder with ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies. Currently, there are only three publications describing mono- and biallelic variants in this gene (PMID: 29496980, 30487246, 35379526). The exact pathophysiological mechanisms are not yet fully understood, but there is a hypothesis that dominant mutations are either gain-of-function or haploinsufficiency and recessive mutations are due to loss-of-function. Most of the described patients have heterozygous de novo variants, and only one family had homozygous loss-of-function variant. We have one patient from consanguineous parents with homozygous ELOVL1 missense variant whose phenotype is compatible with previously reported sibings – motor delay, head tremor, gait ataxia, spasticity, keratoderma, hypomyelination and borderline developmental delay. In this project, we are looking for additional patients with homozygous and bi-allelic ELOVL1 variants, to collect clinical and genetic data and further delineate the full spectrum of this recently described disorder. We will perform lipidomics, and protein and RNA studies on the cells derived from the patients.
Coordinating clinicians
Dr. Tinatin Tkemaladze – t.tkemaladze@tsmu.edu
Dr. Reza Maroofian – r.maroofian@ucl.ac.uk
Institutions
Department of Genetics, Tbilisi State Medical University, Tbilisi, Georgia
Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London, UK
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: Yes
3- Linked to a translational/basic research project: Yes