This report describes mitochondrial complex IV deficiency, nuclear type 1 (MC4DN1); MC4DN1 exhibits autosomal recessive inheritance. The human gene implicated in this disease subtype is SURF1, which encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the assembly of the cytochrome c oxidase (COX) complex. The human SURF1 gene is also implicated in a second disease, Charcot-Marie-Tooth disease, type 4K (MIM:616684). There is a single fly ortholog, Dmel\Surf1, for which RNAi-targeting constructs are available.
The human SURF1 gene has not been introduced into flies.
Depending upon the GAL4 driver used, reduced expression of Dmel\Surf1 effected by RNAi results in lethality or neuroanatomy-defective phenotypes.
[updated Feb. 2021 by FlyBase; FBrf0222196]
Leigh syndrome is an early-onset progressive neurodegenerative disorder; clinical symptoms depend on which areas of the central nervous system are involved. [from MIM:256000; 2016.01.06]
The symptoms of Leigh syndrome usually begin between the ages of three months and two years. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. [from NORD, Leigh Syndrome; 2016.08.12]
Mitochondrial complex IV deficiency (cytochrome c oxidase deficiency) is clinically heterogeneous, ranging from isolated myopathy to severe multisystem disease, with onset from infancy to adulthood. [from MIM:220110; 2016.08.12]
[MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 1; MC4DN1](https://omim.org/entry/220110)
[SURFEIT 1; SURF1](https://omim.org/entry/185620)
Mitochondrial complex IV deficiency nuclear type 1 (MC4DN1) is an autosomal recessive metabolic disorder characterized by rapidly progressive neurodegeneration and encephalopathy with loss of motor and cognitive skills between about 5 and 18 months of age after normal early development. Affected individuals show hypotonia, failure to thrive, loss of the ability to sit or walk, poor communication, and poor eye contact. [from MIM:220110; 2021.02.26]
SURF1 is a nuclear gene; Leigh syndrome, SURF1-related [FlyBase designation] is inherited as an autosomal recessive caused by homozygous or compound heterozygous mutations in this gene.
Mitochondrial complex IV (cytochrome c oxidase) deficiency-1 (MC4DN1) is caused by homozygous or compound heterozygous mutation in the SURF1 gene. [from MIM:220110; 2021.02.26]
SURF1 encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the assembly of the cytochrome c oxidase (COX) complex. [from GeneCards, SURF1; 2016.01.06]
The SURF1 gene encodes an assembly factor of mitochondrial complex IV (COX), the terminal component of the mitochondrial respiratory chain (summary by Echaniz-Laguna et al., 2013; pubmed:24027061). [from MIM:185620; 2016.01.06]
One to one: 1 human to 1 Drosophila (reciprocal best hit).
High-scoring ortholog of human SURF1 (1 Drosophila to 1 human). Dmel\Surf1 shares 44% identity and 58% similarity with human SURF1.
