Intellectual disability - microarray and sequencing
Gene: BSCL2The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.
Panel Version: 4.53
Comment on mode of inheritance: Monoallelic variants lead to a motor neuropathy (MIM# 619112) or spastic paraplegia (MIM# 270685) presentation, both characterised by motor symptoms, but neither are associated with any cognitive deficits. On the other hand, biallelic variants cause encephalopathy (MIM# 615924) or generalised lipodystrophy (MIM# 269700) which do include cognitive decline and intellectual impairment, respectively.
Therefore, the MOI should be changed from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS panel review.Created: 28 Jul 2021, 10:37 a.m. | Last Modified: 28 Jul 2021, 10:37 a.m.
Panel Version: 3.1207
Comment when marking as ready: Developmental regression in first years of life, death within first decade. Age range is within appropriate scope for this panel, therefore include as ID / regression may be presenting feature.Created: 18 Dec 2017, 1:56 p.m.
Intellectual disability is included in the phenotypes of encephalopathy, progressive, with or without lipodystrophy 615924; Lipodystrophy, congenital generalized, type 2 269700. Three biallelic variants were reported in encephalopathy, progressive, with or without lipodystrophy 615924 which includes cognitive decline and death in childhood. The variants were found in one homozygous case and two unrelated compound heterozygotes (one inferred from parental genotypes). Variant c.985C>T p.E329* was identified as a potiential founder variant (PMID 23564749). At least 17 variants reported in Lipodystrophy, congenital generalized, type 2 269700, which includes mild mental retardation (PMID 15181077).Created: 15 Dec 2017, 9:38 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_gilissen_2014_known;in_omim_20150205_movement;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : NACreated: 27 Jul 2017, 5:12 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : gilissen_2014_known; omim_20150205_movement; manju_list; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; NA. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 12:07 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Tag Q3_21_MOI was removed from gene: BSCL2.
Source NHS GMS was added to BSCL2. Mode of inheritance for gene BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BSCL2 were changed from Encephalopathy, progressive, with or without lipodystrophy 615924; Lipodystrophy, congenital generalized, type 2 269700; Neuropathy, distal hereditary motor, type VA 600794; Silver spastic paraplegia syndrome 270685 to Encephalopathy, progressive, with or without lipodystrophy, OMIM:615924; Lipodystrophy, congenital generalized, type 2, OMIM:269700
Tag Q3_21_MOI tag was added to gene: BSCL2.
Mode of inheritance for gene: BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source: Expert Review Red was removed from gene: BSCL2
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Expert Review Green was added to BSCL2. Panel: Intellectual disability Model of inheritance for gene BSCL2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene BSCL2 was set to ['24896178', '26503795', '23564749', ' 15181077']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
BSCL2 was added to Intellectual disabilitypanel. Source: Expert Review Red
BSCL2 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen