Early onset or syndromic epilepsy
Gene: BCORL1
XL SHUVER syndrome. Schuurs-Hoeijmakers et al, 2013 (24123876) - 2 Dutch brothers born of unrelated patients - no seizures - hemizygous missense variant, mum unaff. Shukla et al, 2019 (30941876) - 5 boys from 3 unrelated families. 2 unrelated boys - neither had seizures. Three brothers from an Indian family - more severe phenotype including early onset seizures. All had hemizygous missense variants. Mothers unaff or mildly aff. HGMD Pro -other missense variants listed - associated with autism/schizophrenia.Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Kept rating as Red based on Red post-Webex review from Helen Lord.Created: 9 Sep 2019, 10:16 a.m. | Last Modified: 9 Sep 2019, 10:16 a.m.
Panel Version: 1.314
Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Added BCORL1 to the Genetic epilepsy syndromes panel as a Red gene based on a 2019 paper by Shukla et al (PMID:30941876) who report 5 males from 3 families with ASD, ID/DD and dysmorphic features. Three siblings (patients 3, 4 and 5) had Seizures (at 1 year, 2 year and 6 months of age, respectively). Patients 1 and 2 did not have seizures but their ID/DD phenotype was less severe than those of the three brothers. Therefore currently only one family and a Red rating.
Sources: LiteratureCreated: 6 Jun 2019, 10:34 a.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
Intellectual disability and seizures
Publications
Source Wessex and West Midlands GLH was added to BCORL1.
Source NHS GMS was added to BCORL1.
Phenotypes for gene: BCORL1 were changed from Intellectual disability and seizures to Intellectual disability and seizures; Shukla-Vernon syndrome, 301029
Publications for gene: BCORL1 were set to 30941876
gene: BCORL1 was added gene: BCORL1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: BCORL1 were set to 30941876 Phenotypes for gene: BCORL1 were set to Intellectual disability and seizures