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| White matter disorders and cerebral calcification - narrow panel v2.9 | LIG3 | Sarah Leigh Tag Q2_21_rating was removed from gene: LIG3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v2.9 | LIG3 | Sarah Leigh reviewed gene: LIG3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v2.8 | LIG3 |
Sarah Leigh Source NHS GMS was added to LIG3. Source Expert Review Green was added to LIG3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| White matter disorders and cerebral calcification - narrow panel v1.100 | LIG3 | Ivone Leong Tag Q2_21_rating tag was added to gene: LIG3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v1.100 | LIG3 | Ivone Leong Phenotypes for gene: LIG3 were changed from gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy; mitochondrial DNA depletion | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v1.99 | LIG3 | Ivone Leong Classified gene: LIG3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v1.99 | LIG3 |
Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. PMID:33855352. 3 unrelated families with 7 affected individuals. Clinical features of affected individuals resemble mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). All had severe dysmotility of the gut, leukoencephalopathy and/or progressive cortical atrophy. Cerebella atrophy was only seen in patients in family 3. Other neurological features were epilepsy, stroke-like episodes, migraine and developmental delay. 4 members from families 1 and 2 had macular degeneration, 1 member from family 3 had cataracts and hearing loss. Age of onset and disease severity differed, ranging from paediatric severe disease with premature death to adult cases. All affected members from the 3 families were compound heterozygous for different LIG3 variants. LIG3 variants cause impared ligase activity, mtDNA depletion and mitochondrial dysfunction. The authors also created a zebrafish model, which recapitulated the cerebellar phenotype (seen in mice) and eye defects and gut propulsion impairment (seen in patients). Knockdown of lig3 in zf also led to decrease in expression of mitochondrial markers. Knocking out Lig3 in mice led to early embryonic lethality with mitochondrial dysfunction due to reduced mtDNA in the nervous system (PMID: 21390131); however, gut motility was not investigated in these mice. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review. |
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| White matter disorders and cerebral calcification - narrow panel v1.99 | LIG3 | Ivone Leong Gene: lig3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| White matter disorders and cerebral calcification - narrow panel v1.72 | LIG3 |
Zornitza Stark gene: LIG3 was added gene: LIG3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature Mode of inheritance for gene: LIG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIG3 were set to 33855352 Phenotypes for gene: LIG3 were set to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy Review for gene: LIG3 was set to GREEN Added comment: Seven individuals from three unrelated families and functional data, variable ages of onset from early childhood to late adolescence. Sources: Literature |
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