Likely inborn error of metabolism - targeted testing not possible
Gene: LETM1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 12:32 p.m. | Last Modified: 11 Oct 2023, 12:32 p.m.
Panel Version: 4.51
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 18 May 2023, 12:49 p.m. | Last Modified: 18 May 2023, 12:49 p.m.
Panel Version: 4.35
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: 18 May 2023, 12:39 p.m. | Last Modified: 8 Aug 2023, 10:19 a.m.
Panel Version: 4.44
A lot of functional evidence that this is encodes an important mitochondrial protein; however, no published cases to link to human disease that I can find.Created: 30 Aug 2018, 5:59 a.m.
Tag Q2_23_promote_green was removed from gene: LETM1.
Source NHS GMS was added to LETM1. Source Expert Review Green was added to LETM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: letm1 has been classified as Amber List (Moderate Evidence).
Tag Q2_23_promote_green tag was added to gene: LETM1.
Mode of inheritance for gene: LETM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LETM1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Publications for gene: LETM1 were set to
Sarah Leigh: Associated with phenotype in O
gene: LETM1 was added gene: LETM1 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: LETM1 was set to Unknown Phenotypes for gene: LETM1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)