Mitochondrial disease

Gene: TIMMDC1

Green List (high evidence)

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.

Created: 1 Dec 2022, 4:42 a.m. | Last Modified: 1 Dec 2022, 4:42 a.m.

Panel Version: 0.848

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 31 MIM#618251

Publications

• 36349561
• 33278652

Variants in this GENE are reported as part of current diagnostic practice

I don't know

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

Created: 20 Mar 2020, 4:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 31 MIM#618251

Publications

• 28604674
• 30981218

I don't know

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

Created: 20 Mar 2020, 12:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 31 MIM#618251

Publications

• 28604674
• 30981218