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| Mitochondrial disease v0.850 | TIMMDC1 | Zornitza Stark Classified gene: TIMMDC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.850 | TIMMDC1 | Zornitza Stark Gene: timmdc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.848 | TIMMDC1 |
Paul De Fazio changed review comment from: PMID:36349561 report the same homozygous missense variant p.(Arg137His) was identified in 4 fetuses from 2 families terminated for corpus callosum defects. Autopsies showed global hypotrophy and similar facial dysmorphism with coarse face, microcephaly, and microlissencephaly or gyration delay. All 4 fetuses were diagnosed with complete agenesis of CC. Immunoblot analyses of muscle homogenates revealed a strong reduction in the abundance of the TIMMDC1 protein. There was decreased abundance of complex I subunits in muscle tissue. PMID:33278652 reported two siblings from a Dutch family presenting in infancy with hypotonia and respiratory insufficiency and a rapidly progressive and fatal disease course. A muscle biopsy demonstrated complex I deficiency in brother 2. Each was compound het for the NMD-predicted variant p.(Arg129*) and the previously reported recurrent deep intronic variant c.596+2146A>G. In total, 3 variants in 6 families with mitochondrial complex I deficiency have been reported.; to: PMID:36349561 report the same homozygous missense variant p.(Arg137His) was identified in 4 fetuses from 2 families terminated for corpus callosum defects. Autopsies showed global hypotrophy and similar facial dysmorphism with coarse face, microcephaly, and microlissencephaly or gyration delay. All 4 fetuses were diagnosed with complete agenesis of CC. Immunoblot analyses of muscle homogenates revealed a strong reduction in the abundance of the TIMMDC1 protein. There was decreased abundance of complex I subunits in muscle tissue. PMID:33278652 reported two siblings from a Dutch family presenting in infancy with hypotonia and respiratory insufficiency and a rapidly progressive and fatal disease course. A muscle biopsy demonstrated complex I deficiency in brother 2. Each was compound het for the NMD-predicted variant p.(Arg129*) and the previously reported recurrent deep intronic variant c.596+2146A>G. In total, 3 variants in 6 families with mitochondrial complex I deficiency have been reported. A deep intronic variant shown to affect splicing is recurrent. |
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| Mitochondrial disease v0.848 | TIMMDC1 | Paul De Fazio reviewed gene: TIMMDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36349561, 33278652; Phenotypes: Mitochondrial complex I deficiency, nuclear type 31 MIM#618251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.434 | TIMMDC1 | Zornitza Stark Marked gene: TIMMDC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.434 | TIMMDC1 | Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.225 | TIMMDC1 | Zornitza Stark Tag deep intronic tag was added to gene: TIMMDC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.213 | TIMMDC1 | Bryony Thompson Classified gene: TIMMDC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.213 | TIMMDC1 | Bryony Thompson Gene: timmdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.212 | TIMMDC1 |
Bryony Thompson gene: TIMMDC1 was added gene: TIMMDC1 was added to Mitochondrial disease. Sources: NHS GMS Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674; 30981218 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251 Review for gene: TIMMDC1 was set to AMBER Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect. Sources: NHS GMS |
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