Intellectual disability - microarray and sequencing
Gene: MRE11
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
ATAXIA TELANGIECTASIA-LIKE DISORDER
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_omim_20150205_movement . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 7:38 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; omim_20150205_movement; GEL_ID_red_20160217; 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, 12:52 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Nomenclature history profile of this gene (from correspondence with HGNC) : a change was made in the 1990s of the gene symbol MRE11 to MRE11A which left a withdrawn MRE11 gene symbol even though this was really just a rename. Then, recently, MRE11A was named back to MRE11after MRE11B turned out to be a pseudogene and was renamed to MRE11P1. HGNC will now delete the MRE11 withdrawn symbol so that this confusion will not occur again. There is now only one MRE11 record, with HGNC:7230. Variants of this gene have been confirmed to cause Ataxia-telangiectasia-like disorder, an autosomal recessive movement disorder characterized clinically by progressive cerebellar degeneration resulting in ataxia and oculomotor apraxia (PMID: 10612394, 11371508, 22863007, 15269180). However, Matsumoto Y et al., (2011) PMID: 21227757 found that two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly. Noting that MRE11 and NBN function together as components of a MRE11-RAD50-NBN protein complex, deficiency of either protein did not result in the same clinical features. Mutations in the NBN gene underlie Nijmegen breakage syndrome (NBS), a chromosomal instability syndrome characterized by microcephaly, bird-like faces, growth and mental retardation, and cellular radiosensitivity. Additionally, mutations in the MRE11A gene are known to lead to an ataxia-telangiectasia-like disorder (ATLD), a late-onset, slowly progressive variant of ataxia-telangiectasia without microcephaly. In their study Matsumoto Y et al., (2011) PMID: 21227757 describe two unrelated patients with NBS-like severe microcephaly (head circumference -10.2 SD and -12.8 SD) with mutations just in the MRE11A gene. Both patients were compound heterozygotes for a truncating or missense mutation and carried a translationally silent mutation. The truncating and missense mutations were assumed to be functionally debilitating. The translationally silent mutation common to both patients had an effect on splicing efficiency resulting in reduced but normal MRE11 protein. Comment on phenotypes: phenotype from PMID: 21227757. Comment on list classification: two cases with ID for Nijmegen breakage syndrome-like severe microcephaly, both cases had speech and learning difficulties, however there are other reports with pathogenic variants in patients with conditions such as Hereditary cancer-predisposing syndrome and Microcephaly, normal intelligence and immunodeficiency. Comment on publications: added publication to support association to Nijmegen breakage syndrome-like severe microcephaly.Flagged for clinical team to review - could potentially be Amber based on PMID: 21227757 (2011). However, only a single published study to date and since then (see clinvar) there are many more cases but with other associated conditions with : Microcephaly, normal intelligence and immunodeficiency (ID is normal) and is linked to Hereditary cancer-predisposing syndrome. Clinical team review confirmed this gene should remain rated as Red on the ID panel. HB noted that although ID can be a feature there are usually other clues re DNA repair disorders. Gene added as Amber to Cockayne and Xeroderna Pigmentosum-like disorder and New gene for Primary Microcephaly - Microcephalic Dwarfism Spectrum panels.Created: 12 Mar 2018, 9:47 a.m.
Nomenclature history profile of this gene (from correspondence with HGNC) : a change was made in the 1990s of the gene symbol MRE11 to MRE11A which left a withdrawn MRE11 gene symbol even though this was really just a rename. Then, recently, MRE11A was named back to MRE11after MRE11B turned out to be a pseudogene and was renamed to MRE11P1. HGNC will now delete the MRE11~withdrawn symbol so that this confusion will not occur again. There is now only one MRE11 record, with HGNC:7230.Created: 20 Jul 2017, 2:56 p.m.
added new-gene-name tag. New approved HGNC gene symbol is MRE11.Created: 20 Jul 2017, 2:56 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Nijmegen breakage syndrome-like severe microcephaly, Intellectual disability
Publications
Comment on list classification: Not an ID phenotypeCreated: 7 Feb 2016, 11:30 p.m.
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.
Publications for gene MRE11 was set to ['21227757']
MRE11A was changed to MRE11
new-gene-name was removed from MRE11A. Panel: Intellectual disability
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
MRE11A was created by ellenmcdonagh
MRE11A was added to Intellectual disabilitypanel. Sources: Expert Review Amber