Intellectual disability - microarray and sequencing
Gene: RARB
More than 10 unrelated families reported with microphthalmia and diaphragmatic hernia. Long-term survivors have ID. Some evidence for GoF for heterozygous missense variants.Created: 6 Dec 2022, 10:01 a.m. | Last Modified: 6 Dec 2022, 10:01 a.m.
Panel Version: 4.2
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Microphthalmia, syndromic 12, MIM# 615524; Neurodevelopmental disorder
Publications
OMIM has description only for anophtalmia, but gain-of-Function Mutations in RARB Cause Intellectual Disability with Progressive Motor Impairment.Created: 29 Nov 2022, 3:22 p.m. | Last Modified: 29 Nov 2022, 3:22 p.m.
Panel Version: 3.1771
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Intellectual Disability with Progressive Motor Impairment
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA
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_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 . Main mutation mechanism : Loss of function; Dominant negativeCreated: 27 Jul 2017, 8:13 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function; Dominant negative. 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, 1:14 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
Mode of pathogenicity
Comment on list classification: ID present in sole surviving reported case. Other features would be expected to be presentCreated: 8 Feb 2016, 12:30 a.m.
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from None to None
Mode of pathogenicity for gene: RARB was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Publications for gene: RARB were set to 24075189
Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Mode of pathogenicity for gene: RARB was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Source Victorian Clinical Genetics Services was added to RARB.
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 Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
RARB was created by ellenmcdonagh
RARB was added to Intellectual disabilitypanel. Sources: Expert Review Amber