Early onset or syndromic epilepsy

Gene: HCFC1

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

XLR mental retardation 3 (methylmalonic acidemia and homocystinemia cbIX type) - characterised by severely delayed psychomotor development apparent in infancy - it is associated with failure to thrive, mental retardation and intractable epilepsy. Yu et al, 2013 - 14 unrelated makes with severe delayed psychomotor development and intractable epilepsy - 5 diff hemizygous missense variants - 9 have the A115V variant and all variants are at highly conserved residues in 2 of the 5 N-terminal Kelch domains, some functional work done.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), 309541

Publications

• 24011988
• 26893841

Comment when marking as ready: Mental retardation, X-linked 3 is associated with HCFC1 and is confirmed in both OMIM and Gene2Phenotype. >3 unrelated probands have been found to have a mutation in this gene or its regulatory site and also have epilepsy.

Created: 14 Nov 2018, 2:12 p.m.

Comment on list classification: Promoted from amber to green as >3 unrelated probands have been found to have a mutation in this gene and also have epilepsy.

Created: 14 Nov 2018, 2:11 p.m.

Green List (high evidence)

Seizures are part of the phenotype.

Created: 15 Aug 2018, 12:45 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), MIM#309541

Publications

• 24011988

Variants in this GENE are reported as part of current diagnostic practice