Early onset or syndromic epilepsy
Gene: TBL1XR1
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
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.
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
Source Wessex and West Midlands GLH was added to TBL1XR1.
Source NHS GMS was added to TBL1XR1.
Zornitza Stark: Seizures are reported in a pro
Gene: tbl1xr1 has been classified as Green List (High Evidence).
Gene: tbl1xr1 has been classified as Green List (High Evidence).
Publications for gene: TBL1XR1 were set to
Mode of inheritance for gene: TBL1XR1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TBL1XR1 were changed from to Mental retardation, autosomal dominant 41, 616944; Pierpont syndrome, 602342
Expert Review Amber was added to TBL1XR1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to TBL1XR1. Panel: Genetic Epilepsy Syndromes
TBL1XR1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert Review
TBL1XR1 was created by Sarah Leigh