Gene/phenotype/disorder under study
ITFG2 (MIM 617421)
Abstract
ITFG2 encodes integrin alpha FG-GAP repeat-containing protein 2, a component of the KICSTOR complex with SZT2, KPTN, and KICS2, a negative regulator of mTORC1 signaling. Disruption of this pathway may cause mTORC1 overactivation and neurodevelopmental disease within the spectrum of mTORopathies.
While biallelic variants in SZT2, KPTN and KICS2 are established causes of intellectual disability, epilepsy, and macrocephaly, the clinical significance of biallelic ITFG2 variants remains poorly defined. Only a few cases have been reported to date, and ITFG2 is not yet fully established as a disease gene, with no current OMIM entry.
We have collected over 30 families with biallelic ITFG2 variants, comprising 23 distinct variants including four recurrent variants. Preliminary features include developmental delay, intellectual disability, autistic features, macrocephaly, short stature, dysmorphism, and short/thick corpus callosum in some cases.
We invite clinicians and researchers with ITFG2-related NDD cases to contact us to share genetic, clinical, and neuroimaging data and collaborate on phenotype delineation and genotype-phenotype correlations.
Coordinating team
Dr Reza Maroofian – r.maroofian@ucl.ac.uk
Dr Aicha Kalfat – aicha.kalfat@gmail.com
Pr Henry Houlden – h.houlden@ucl.ac.uk
Institution
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
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: No