Severe microcephalyGene: MRE11
Comment on list classification: added new gene as Amber, In view of the marked microcephaly and other breakage disorder phenotypes this gene was added to the panel but there is only single reported paper for relevant phenotype
8 Mar 2018, 3:46 p.m.
added watchlist tag
8 Mar 2018, 3:45 p.m.
Gene added as part of the ID panel review. 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gene (from correspondence with HGNC) : a change was made in the 1990s of the gene symbol MRE11 to MRE11A which left a withdrawn MRE11 gene symbol even though this was really just a rename.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 HGNC will now delete the MRE11~withdrawn symbol so that this confusion will not occur again.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.
8 Mar 2018, 3:45 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Nijmegen breakage syndrome-like severe microcephaly
This gene has been classified as Amber List (Moderate Evidence).
MRE11 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrum panel. Sources: Literature
MRE11 was created by Louise Daugherty