Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency

Jackson, Christopher; Nuoffer, Jean-Marc; Hahn, Dagmar Karen; Prokisch, Holger; Haberberger, Birgit; Gautschi, Matthias; Haeberli, Annemarie; Gallati, Sabina; Schaller, André (2013). Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency. Journal of medical genetics, 51(3), pp. 170-175. BMJ Publishing Group 10.1136/jmedgenet-2013-101932

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik

UniBE Contributor:

Jackson, Christopher; Nuoffer, Jean-Marc; Hahn, Dagmar Karen; Gautschi, Matthias; Haeberli, Annemarie; Gallati, Sabina and Schaller, André

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-2593

Publisher:

BMJ Publishing Group

Language:

English

Submitter:

André Schaller

Date Deposited:

07 Feb 2014 10:43

Last Modified:

26 Jun 2016 01:46

Publisher DOI:

10.1136/jmedgenet-2013-101932

PubMed ID:

24367056

Uncontrolled Keywords:

SDHD complex II deficiency, encephalopathy, mitochondrial disorder, succinate dehydrogenase

BORIS DOI:

10.7892/boris.39939

URI:

https://boris.unibe.ch/id/eprint/39939

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