Early onset or syndromic epilepsy

Gene: IQSEC2

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)

X-linked dom mental retardation 1 (MRX1). OMIM lists seizures seen in some patients. Suthers et al 1988 - large family with multiple males spannig generations affected - 1 had infrequent seizures. Shoubridge et al 2010 - some affecteds had seizures. Aff members of 4 unrelated families - 4 diff hemizygous variants. Tran Mau-Them, 2014 - 3 unrelated males - 2 developed seizures - 3 diff mutations detected - 2 led to premature termination and 1 was nonsense. De Vries et al, 2002 & Kalscheuer et al, 2016 - 6 aff males, 7 aff females, 2 males had epilepsy and 1 a single seizure - missense variant detected, expression studies supported pathogenicity. On HGMD Pro - more cases associating this gene with an epilepsy phenotype - Zerem et al, 2016, Hamdan et al, 2017.

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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 26793055
• 23674175

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• Shoubridge et al (2010) Nat Genet 42(6): 486-8

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• Shoubridge et al (2010) Nat Genet 42(6): 486-8

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• Shoubridge et al (2010) Nat Genet 42(6): 486-8

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

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• Shoubridge et al (2010) Nat Genet 42(6): 486-8

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

Comment on mode of inheritance: Checked the mode of inheritance with the reviewer to confirm.

Created: 20 Jan 2016, 12:08 p.m.

Comment on phenotypes: Phenotype from OMIM.

Created: 20 Jan 2016, 12:06 p.m.

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).

Created: 12 Nov 2015, 4:18 p.m.