Early onset or syndromic epilepsy

Gene: TBL1XR1

Green List (high evidence)

AD Pierpont syndrome and AD mental retardation. Both can present with seizures (panel app). Pierpont syndrome - 7 unrelated patients all have the same variant Y446C - no specific mention of epilepsy in these on OMIM says seizures are seen in some patients. AD-MR on OMIM it says seizures - 1 patient. On panel app it links to a 2018 paper where one patient had seizures and anpther patient didn't.

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

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation autosomal dominant 41, 616944; Pierpont syndrome, 602342

Publications

• 25102098

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

Comment on list classification: Updated rating from Amber to Green: Confirmed DD-G2P gene for Pierpont and mental retardation, both of which can present with seizures. Seizures reported in at least 3 patients (PMID:25102098, PMID:30365874 and PMID:9450851-original patient). Burkitt Wright, 2011 (PMID:21834056) also reports that "Seizures, in particular absence seizures, have been reported in several [Pierpont] patients. While they are clearly not universal, it currently appears that epilepsy may be sufficiently more common in children with Pierpont syndrome to be considered a feature of the condition". Therefore reasonable to include TBL1XR1 on the diagnostic panel.

Created: 8 Nov 2018, 11 a.m.

Previously reported individuals reported by Burkitt Wright, 2011 (PMID:21834056) include the initial patient reported by Pierpont et al 1998 (PMID:9450851) who had grand mal seizures from age 5.

Created: 8 Nov 2018, 10:05 a.m.

PMID:30365874 (Lemattre et al 2018) report a Caucasian boy (Patient 1) with a seizure disorder with both myoclonic and focal seizures that began age 10. Her harboured a de novo heterozygous missense variant (NM_024665.4:c.974G>A, p.Cys325Tyr) in TBL1XR1. Their second unrelated patient also had a missense TBL1XR1 variant but never had seizures.

Created: 8 Nov 2018, 10:05 a.m.

In a 5-year-old Japanese girl with autosomal dominant mental retardation-41 (MRD41; 616944), Saitsu et al. (2014, PMID:25102098) identified a de novo heterozygous transition (c.209G-A, NM_024665.4) in the TBL1XR1 gene (G70D). The patient developed infantile spasms at age 5 months.

Created: 8 Nov 2018, 10:04 a.m.

PMID:29777588 (Zahlula et al 2018) summarises phenotypes of patients with TBL1XR1 variants, including seizures.

Created: 8 Nov 2018, 10:04 a.m.

Green List (high evidence)

Seizures are reported in a proportion of patients with Pierpoint syndrome, and also in some patients with other TBL1XR1 variants causing ID.

Created: 22 Aug 2018, 5:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pierpont syndrome, MIM#602342; Mental retardation, autosomal dominant 41, MIM#616944

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)