Intellectual disability - microarray and sequencing
Gene: BCORL1Comment on list classification: Kept rating Amber in line with the previous review by Rebecca Foulger. Severe ID only exhibited by 2/4 families. No additional papers recently published.Created: 13 Oct 2020, 9:29 a.m. | Last Modified: 13 Oct 2020, 9:29 a.m.
Panel Version: 3.430
Four unrelated families reported with variable ID, now has OMIM#, and original variant no longer listed as VOUS.Created: 29 Jan 2020, 10:25 a.m. | Last Modified: 29 Jan 2020, 10:25 a.m.
Panel Version: 3.0
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Shukla-Vernon syndrome, MIM# 301029
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Updated rating from Red to Amber based on external review by Konstantinos Varvagiannis and the new paper Shukla et al., 2019 (PMID:30941876). The original Asn820Ser variant from Schuurs-Hoeijmakers et al., 2013 (PMID:24123876) is still listed as a VUS in OMIM due to a lack of evidence for association with the ID phenotype. Although Shukla et al report 3 cases with 3 new BCORL1 variants (two unrelated males and a further three brothers), patient 2 does not have ID, but instead has typical early motor milestones, and speech delay. ID is also mild in Patient 1. Based on 2 clear cases plus 1 potential case from Shukla et al,. I have rated Amber and added a 'watchlist' tag awaiting further reports.Created: 6 Jun 2019, 10:27 a.m.
This gene may be considered for upgrade probably to amber (or green).
Schuurs-Hoeijmakers et al. (2013 - PMID: 24123876) reported briefly on 2 males with hypotonia, severe ID and similar facial features. Both harbored a BCORL1 missense variant (NM_021946.4:c.2459A>G or p.Asn820Ser) inherited from their (probably) unaffected mother (X-linked gene). The authors comment that BCORL1 encodes a transcriptional corepressor interacting with class II histone acetyltransferases and deacetylases and appears to be expressed in brain/neuronal tissue.
Shukla et al. (2019 - PMID: 30941876) report on 5 males from 3 families with DD, ID (4/5 - in 1 individual mild, in 3 further sibs severe), ASD (5/5) or additional behavioral abnormalities and/or some other possibly overlapping features. All individuals were found to be hemizygous for BCORL1 missense variants (in all cases inherited). The following variants were reported : c.2345T>A or p.Val782Glu, c.1487C>T or p.Ser496Phe and c.95C>T or p.Pro32Leu (NM_021946.4). The mother of one subject (with mild ID) had some degree of learning disabilities, anxiety and ADHD. One individual without apparent ID had inherited the variant from his mother who had normal educational attainment.
There are no functional studies (or X-inactivation studies in females) performed in any of these articles.
BCORL1 is not associated with any phenotype in OMIM/G2P. The gene is included in gene panels for intellectual disability offered by several diagnostic laboratories (incl. Radboud UMC).Created: 14 Apr 2019, 6:07 p.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
Global developmental delay; Intellectual disability; Autism; Behavioral abnormality
Publications
Variants in this GENE are reported as part of current diagnostic practice
Not associated with phenotype in OMIM or G2P. One variant reported as a heterozygote in two brothers with severe intellectual disability, however also present in unaffected mother, therefore classes as a VUSCreated: 15 Dec 2017, 9:38 a.m.
Mode of inheritance
Unknown
Publications
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 for gene: BCORL1 were changed from Intellectual disability, developmental delay and dysmorphism; Behavioral abnormality to Shukla-Vernon syndrome, 301029
Publications for gene: BCORL1 were set to 24123876; 24896178; 26350204; 30941876
Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: BCORL1.
Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Publications for gene: BCORL1 were set to 24123876; 24896178; 26350204
Phenotypes for gene: BCORL1 were changed from to Intellectual disability, developmental delay and dysmorphism; Behavioral abnormality
Mode of inheritance for gene: BCORL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
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.
Model of inheritance for gene BCORL1 was set to Unknown Publications for gene BCORL1 was set to ['24123876', ' 24896178', ' 26350204']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
BCORL1 was added to Intellectual disabilitypanel. Sources: Expert Review Red
BCORL1 was created by ellenmcdonagh