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Possible mitochondrial disorder - nuclear genes

Gene: LETM1

Green List (high evidence)

LETM1 (leucine zipper and EF-hand containing transmembrane protein 1)
EnsemblGeneIds (GRCh38): ENSG00000168924
EnsemblGeneIds (GRCh37): ENSG00000168924
OMIM: 604407, Gene2Phenotype
LETM1 is in 14 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 4 Dec 2024, 11:42 a.m. | Last Modified: 4 Dec 2024, 11:42 a.m.
Panel Version: 3.113

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

LETM1 variants have been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).
Created: 3 Aug 2023, 10:07 a.m. | Last Modified: 8 Aug 2023, 10:16 a.m.
Panel Version: 3.42
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 3 Aug 2023, 9:16 a.m. | Last Modified: 3 Aug 2023, 9:16 a.m.
Panel Version: 3.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Carl Fratter (Oxford University Hospitals NHS Trust)

Green List (high evidence)

Consensus opinion from the 3 NHSE GMS specialist mitochondrial providers.
Sources: Expert Review
Created: 31 Jul 2023, 10:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
620089 Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction

History Filter Activity

4 Dec 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: LETM1. Tag Q3_23_NHS_review was removed from gene: LETM1.

4 Dec 2024, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to LETM1. Source NHS GMS was added to LETM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

2 Jul 2024, Gel status: 2

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_MOI was removed from gene: LETM1.

3 Aug 2023, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_23_NHS_review tag was added to gene: LETM1.

3 Aug 2023, Gel status: 2

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_23_promote_green tag was added to gene: LETM1. Tag Q3_23_MOI tag was added to gene: LETM1.

3 Aug 2023, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: letm1 has been classified as Amber List (Moderate Evidence).

3 Aug 2023, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: LETM1 were set to

3 Aug 2023, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: LETM1 were changed from 620089 Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089

31 Jul 2023, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Carl Fratter (Oxford University Hospitals NHS Trust)

gene: LETM1 was added gene: LETM1 was added to Possible mitochondrial disorder - nuclear genes. Sources: Expert Review Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LETM1 were set to 620089 Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction Review for gene: LETM1 was set to GREEN