Targeted gene under study:

HCFC1 (OMIM # 309541)


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 –,


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