Intellectual disability - microarray and sequencing
Gene: EFNB1
Comment on list classification: Upgrading from Red to Amber as a literature search did reveal evidence to suggest that some individuals may develop intellectual deficits. However, in most affected cases this was a mild presentation and there are more prominent and recognisable features observed in the general group of EFNB1-related cases which are more likely to inform diagnostic testing (e.g. craniosynostosis and clefting).Created: 29 Feb 2024, 4:41 p.m. | Last Modified: 29 Feb 2024, 4:41 p.m.
Panel Version: 5.474
Comment on publications: PMID: 25679214 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniquesCreated: 29 Feb 2024, 2:28 p.m. | Last Modified: 29 Feb 2024, 2:28 p.m.
Panel Version: 5.473
This gene causes craniofrontonasal syndrome (CFNS) - a predominantly craniosynostosis phenotype with various limb features. Cognitive function is usually unaffected; however, some cases have been observed:
- PMID: 23335590 (2013) - describes six males with CFNS due to mosaic EFNB1 variants. Mild learning disability was reported for 5/6.
- PMID: 25679214 (2015) - EFNB1 variant (p.G290R) was found in an individual from a X-linked Intellectual Disability cohort. Limited information so it is unclear if this patient had additional features of CFNS.
- PMID: 27650623 (2016) - one patient with a c.451G>A (p.Gly151Ser) variant in EFNB1 showed borderline intellectual functioning (IQ = 76) along with other typical features such as unilateral coronal synostosis, cleft palate, and septate uterus. On the other hand, the other patient described in this paper had normal developmental milestones.
- PMID: 31088393 (2019) - a de novo heterozygous variant c.640C > T; p.(Gln214Ter) in EFNB1 was detected in a girl with severe ID, typical facial dysmorphia, ocular anomalies, short fifth finger, cerebellar vermis dysplasia and fourth ventricle deformity.
- PMID: 24520368 (2014) - EphrinB1 deficient mouse model of CFNS shows cortical abnormalities and impaired non-spatial learning and memory tasksCreated: 29 Feb 2024, 2:27 p.m. | Last Modified: 29 Feb 2024, 2:27 p.m.
Panel Version: 5.472
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
Craniofrontonasal dysplasia, OMIM:304110
Publications
Comment when marking as ready: Normal intellect expected.Created: 19 Dec 2017, 3:09 p.m.
Comment on list classification: Normal intellect is expected in Craniofrontonasal syndrome.Created: 19 Dec 2017, 3:08 p.m.
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_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_UKGTN_v12 . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 5:37 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; UKGTN_v12; neuro_20160418_strict; Loss of function. 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, 12:20 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)
Publications
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.Created: 20 Jul 2017, 11:44 a.m.
Gene: efnb1 has been classified as Amber List (Moderate Evidence).
Publications for gene: EFNB1 were set to 23335590
Phenotypes for gene: EFNB1 were changed from Gene2Phenotype confirmed gene with ID HPO to Craniofrontonasal dysplasia, OMIM:304110
Publications for gene: EFNB1 were set to
Source Victorian Clinical Genetics Services was added to EFNB1.
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.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Amber List (Moderate Evidence).
EFNB1 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene
EFNB1 was created by BRIDGE