This report describes :mitochondrial complex II deficiency, nuclear type 4 (MC2DN4); MC2DN4 exhibits autosomal recessive inheritance. The human gene implicated in this disease is SDHB, a subunit of mitochondrial complex II. Mitochondrial complex II, also known as succinate:ubiquinone oxidoreductase or succinate dehydrogenase, participates in both the citric acid cycle and the electron transport chain. It is formed from four subunits: catalytic subunits SDHA and SDHB, and anchoring subunits SDHC and SDHD. SDHB is also linked to increased occurrence of multiple types of tumor (see MIM:185470).
The fly orthologs of both SDH catalytic subunits have been studied in the context of disease: Dmel\SdhA, which is ortholgous to SDHA (see FBhh0001108) and Dmel\SdhB, which is orthologous to SDHB (this report). For SdhB, RNAi targeting constructs, an expression construct, and multiple insertions have been generated.
The human SDHB gene has not been introduced into flies.
Dmel\SdhB mutants have shorter lifespans and climbing defects compared to controls. Both of these phenotypes are improved by treatment with rapamycin, which also slightly decreases hydrogen peroxide production in SdhB mutants.
[updated Jun. 2021 by FlyBase; FBrf0222196]
Mitochondrial complex II deficiency is an autosomal recessive multisystemic metabolic disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, and muscle with onset in infancy, whereas others have only isolated cardiac or muscle involvement. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013; pubmed:23322652). [from MIM:252011; 2021.06.15]
[MITOCHONDRIAL COMPLEX II DEFICIENCY, NUCLEAR TYPE 4; MC2DN4](https://omim.org/entry/619224)
[SUCCINATE DEHYDROGENASE COMPLEX, IRON-SULFUR SUBUNIT B; SDHB](https://omim.org/entry/185470)
Mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is a severe autosomal recessive disorder characterized by early-onset progressive neurodegeneration with leukoencephalopathy. Acute episodes of neurodegeneration are often triggered by catabolic stress such as infection or fasting. [from MIM:619224; 2021.06.15]
Mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is caused by homozygous or compound heterozygous mutation in the succinate dehydrogenase complex subunit B gene (SDHB). [from MIM:619224; 2021.06.15]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human SDHB. There is another moderately-scoring ortholog in flies, SdhBL, but it is expressed largely in testis.
