Early onset or syndromic epilepsy
Gene: HNRNPH2
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
The failure to identify affected males, the severity of the neurodevelopmental phenotype in females, and the essential role of this gene suggests that male conceptuses with these variants may not be viableCreated: 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Mental retardation, X-linked, syndromic, Bain type,300986
Publications
Comment on list classification: changed from red to green due to evidence in the literatureCreated: 19 Dec 2017, 12:14 p.m.
Added from Intellectual disability panel update as gene is also relevant to this panelCreated: 19 Dec 2017, 12:11 p.m.
Bain et al. (2016) PMID: 27545675 reported 5 unrelated female patients with the Bain type of X-linked syndromic mental retardation patients who were shown to manifest psychomotor development, intellectual disability with behavioral abnormalities, and dysmorphic facial features. Additional variable features include musculoskeletal abnormalities, seizures, acquired microcephaly, and feeding problems with poor overall growth. Only females are affected. Bain et al. (2016) also noted that all mutations affected highly conserved residues in the nuclear localization sequence, and postulated a toxic gain-of-function effect, suggesting that these variants may be lethal in males.Created: 19 Dec 2017, 12:11 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Mental retardation, X-linked, syndromic, Bain type, 300986; MRXSB
Publications
Source Wessex and West Midlands GLH was added to HNRNPH2.
Source NHS GMS was added to HNRNPH2.
Louise Daugherty: Bain et al. (2016) PMID: 27545
HNRNPH2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Other
HNRNPH2 was created by Sarah Leigh