Targeted gene under study:
HCFC1 (OMIM # 309541)
Abstract
HCFC1 pathogenic variants were associated with X-linked cobalamin metabolism disorder (CMD), characterized by epileptic encephalopathy with intellectual disability (ID), as well as nonsyndromic ID with/without epilepsy but without CMD.
Exome sequencing identified a hemizygous variant of uncertain significance in HCFC1 in three patients, including siblings, who presented with non-syndromic moderate ID, no CMD or epilepsy. The patients’ asymptomatic carrier mothers show a completely skewed X-inactivation.
We aim to identify more patients carrying hemizygous HCFC1 variants (uncertain significance, probably pathogenic and pathogenic), with or without CMD, to further delineate the HCFC1 variants-associated phenotypes and to evaluate the contribution of X-inactivation carrier mothers’ results in helping to reclassify variants.
Coordinating clinicians
Salima EL CHEHA – salima.elchehadeh@chru-strasbourg.fr, apiton@unistra.fr
Institution
Service de Génétique Médicale, Institut de Génétique Médicale d’Alsace (IGMA), Hôpitaux Universitaires de Strasbourg, Strasbourg, France
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