Paediatric pseudo-obstruction syndrome
Gene: LIG3
The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 7:44 a.m. | Last Modified: 1 Feb 2023, 7:44 a.m.
Panel Version: 0.216
Comment on rating: The rating should be GREEN as this gene has been implicated in mitochondrial neurogastrointestinal encephalomyopathy syndrome (MIM #619780) from seven patients from three unrelated families, and supported by functional studies.
These patients harboured compound heterozygous variants (family 1: p.K537N & p.G964R; family 2: p.C999Y & p.R267Ter; family 3: p.P609L & p.R811Ter) and their clinical phenotypes resembled the mitochondrial MINGE disease in many aspects. Severe dysmotility of the gut was present in all patients and most patients fulfilled the diagnostic criteria for CIPO.
Evidence from skeletal muscle biopsies from patients from all three families showed mitochondrial dysfunction. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. In addition, LIG3 gene defects result in mitochondrial DNA depletion.
In vivo modelling of LIG3 mutations in zebrafish model also reproduced the brain alterations and impaired gut transit.
This gene has already been reported in OMIM.Created: 21 Dec 2022, 11:53 a.m. | Last Modified: 21 Dec 2022, 11:54 a.m.
Panel Version: 0.62
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780
Publications
Review submitted on behalf of Dr. Anna Rybak and Dr. Osvaldo Borreli, Great Ormond Street Hospital for Children NHS Foundation Trust. Gene group: Mitochondrial depletion disorders (MNGIE, MELAS, myopathy, other). Protein function: mitochondrial DNA (mtDNA) replication and maintenance.Created: 20 Dec 2022, 3:32 p.m. | Last Modified: 20 Dec 2022, 3:32 p.m.
Panel Version: 0.2
Mode of inheritance
Unknown
Publications
Phenotypes for gene: LIG3 were changed from to Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780
Publications for gene: LIG3 were set to
Mode of inheritance for gene: LIG3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: lig3 has been classified as Green List (High Evidence).
gene: LIG3 was added gene: LIG3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list Mode of inheritance for gene: LIG3 was set to