Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency

Mitochondrial diseases affect both children and adults and are clinically and genetically diverse, on account of the dual genetic control of mitochondrial function. Isolated complex II deficiency is a rare form of mitochondrial disease, due to autosomal recessive mutations in either structural components of this enzyme (the SDHA, SDHB, SDHC and SDHD genes) or two known assembly factors (SDHAF1 and SDHAF2). Interestingly, these genes are also implicated in tumour formation with germline and somatic mutations known to cause hereditary cancers including paraganglioma and pheochromocytoma. We describe two families with novel mutations in the SDHA and SDHB genes, in which affected children present with a leukodystrophy (brain white matter disease), and for the first time show that SDHB mutation can cause a primary mitochondrial, neurological phenotype in the absence of tumours. Studies in yeast confirm that the new mutation is disease-causing in humans. (By R.W. Taylor PhD, DSc, FRCPath, http://jmg.bmj.com/content/49/9/569 )