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Intellectual disability

Gene: MTO1

Green List (high evidence)

MTO1 (mitochondrial tRNA translation optimization 1)
EnsemblGeneIds (GRCh38): ENSG00000135297
EnsemblGeneIds (GRCh37): ENSG00000135297
OMIM: 614667, Gene2Phenotype
MTO1 is in 9 panels

4 reviews

Catherine Snow (Genomics England)

Green List (high evidence)

Individuals with variants in the MTO1 genes present with a broad phenotype and a broad age, from fatal presentation in the neonatal period to an 8-year-old presenting with ID. GDD/ID affected 28/29, cases for whom this information was available.

PMID 29331171 reports and summarises 35 patients from 26 unrelated families, they reported 19 different MTO1 variants (7 of which had been published and 12 unpublished) of which 15 missense, 3 frameshifts and one splice-site. Of the 35 patients, 17 are homozygous and 13 compound heterozygous for missense variants, four are compound heterozygous for a missense and a frameshift variant and one is compound heterozygous for a missense and a predicted splice-site variant

MTO1 is associated with relevant phenotypes in OMIM and is confirmed in Gene2Phenotype as MTO1 Disease: INFANTILE HYPERTROPHIC CARDIOMYOPATHY AND LACTIC ACIDOSIS although ID is not listed as a phenotype. There are now sufficient number of unrelated cases to give MTO1 a Green rating.
Created: 29 Jul 2019, 9:55 a.m. | Last Modified: 29 Jul 2019, 9:55 a.m.
Panel Version: 2.982

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID 29331171 is a collaborative study reporting on 35 individuals with MTO1 deficiency, 18 of whom were previously published and 17 unpublished. All the cases reported were molecularly confirmed (details are provided for each case, as well as in silico predictions and ExAC frequencies for the variants). Common features include lactic acidosis, hypertrophic cardiomyopathy and mild to severe DD/ID (in 97%). Seizures were present in 34% of the cases. Even if the presentation is highly suggestive, diagnosis may not be straightforward (only 62% had lactate measurements upon initial presentation, few did not have respiratory chain analysis while this came out normal in 3 individuals, HCM was absent in 6 patients, age at presentation was highly variable ranging from 1 day to 8 years).
Created: 13 Aug 2018, 5:03 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 10, 614702

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

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
Created: 27 Jul 2017, 7:41 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; 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 Trust
Created: 19 Jul 2017, 12:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Louise Daugherty (Genomics England Curator)

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, 12:51 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Combined oxidative phosphorylation deficiency 10, 614702
OMIM
614667
Clinvar variants
Variants in MTO1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Jul 2019, Gel status: 3

Set publications

Catherine Snow (Genomics England)

Publications for gene: MTO1 were set to

29 Jul 2019, Gel status: 3

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: mto1 has been classified as Green List (High Evidence).

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

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.

20 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

19 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

MTO1 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

19 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

MTO1 was created by BRIDGE