RT Journal Article SR Electronic T1 Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 170 OP 175 DO 10.1136/jmedgenet-2013-101932 VO 51 IS 3 A1 Christopher Benjamin Jackson A1 Jean-Marc Nuoffer A1 Dagmar Hahn A1 Holger Prokisch A1 Birgit Haberberger A1 Matthias Gautschi A1 Annemarie Häberli A1 Sabina Gallati A1 André Schaller YR 2014 UL http://jmg.bmj.com/content/51/3/170.abstract AB Background Defects of the mitochondrial respiratory chain complex II (succinate dehydrogenase (SDH) complex) are extremely rare. Of the four nuclear encoded proteins composing complex II, only mutations in the 70 kDa flavoprotein (SDHA) and the recently identified complex II assembly factor (SDHAF1) have been found to be causative for mitochondrial respiratory chain diseases. Mutations in the other three subunits (SDHB, SDHC, SDHD) and the second assembly factor (SDHAF2) have so far only been associated with hereditary paragangliomas and phaeochromocytomas. Recessive germline mutations in SDHB have recently been associated with complex II deficiency and leukodystrophy in one patient. Methods and results We present the clinical and molecular investigations of the first patient with biochemical evidence of a severe isolated complex II deficiency due to compound heterozygous SDHD gene mutations. The patient presented with early progressive encephalomyopathy due to compound heterozygous p.E69 K and p.*164Lext*3 SDHD mutations. Native polyacrylamide gel electrophoresis and western blotting demonstrated an impaired complex II assembly. Complementation of a patient cell line additionally supported the pathogenicity of the novel identified mutations in SDHD. Conclusions This report describes the first case of isolated complex II deficiency due to recessive SDHD germline mutations. We therefore recommend screening for all SDH genes in isolated complex II deficiencies. It further emphasises the importance of appropriate genetic counselling to the family with regard to SDHD mutations and their role in tumorigenesis.