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Case Reports
. 2021 Oct;29(10):1570-1576.
doi: 10.1038/s41431-021-00887-w. Epub 2021 May 20.

Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency

Siying Lin #  1 , James Fasham #  1   2 , Fida' Al-Hijawi #  3 , Nouar Qutob  4 , Adam Gunning  1 , Joseph S Leslie  1 , Lucy McGavin  5 , Nishanka Ubeyratna  1 , Wisam Baker  6 , Ramez Zeid  7 , Peter D Turnpenny  2 , Andrew H Crosby  1 , Emma L Baple  8   9 , Reham Khalaf-Nazzal  10
Affiliations
Case Reports

Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency

Siying Lin et al. Eur J Hum Genet. 2021 Oct.

Abstract

Isolated mitochondrial complex II deficiency is a rare cause of mitochondrial respiratory chain disease. To date biallelic variants in three genes encoding mitochondrial complex II molecular components have been unequivocally associated with mitochondrial disease (SDHA/SDHB/SDHAF1). Additionally, variants in one further complex II component (SDHD) have been identified as a candidate cause of isolated mitochondrial complex II deficiency in just two unrelated affected individuals with clinical features consistent with mitochondrial disease, including progressive encephalomyopathy and lethal infantile cardiomyopathy. We present clinical and genomic investigations in four individuals from an extended Palestinian family with clinical features consistent with an autosomal recessive mitochondrial complex II deficiency, in which our genomic studies identified a homozygous NM_003002.3:c.[205 G > A];[205 G > A];p.[(Glu69Lys)];[(Glu69Lys)] SDHD variant as the likely cause. Reviewing previously published cases, these findings consolidate disruption of SDHD function as a cause of mitochondrial complex II deficiency and further define the phenotypic spectrum associated with SDHD gene variants.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Family pedigree showing SDHD c.205 G > A genotype data, neuroimaging and images of affected individuals.
A Pedigree diagram showing segregation of the SDHD c.205 G > A; p.(Glu69Lys) variant. Genotypes are shown beneath generations IV and V (+, c.205 G > A; −, WT). Affected individuals were homozygous for SDHD c.205 G > A, DNA was available from all but one affected individual (V:5). B Electropherogram showing the DNA sequence at the position of SDHD c.205 G > A in a homozygous affected individual. C T1- and T2-weighted axial views of MRI head of individual V:2 (aged 8 months). Normal myelination and no intracranial abnormalities. D Image of affected individual V:4, illustrating the absence of any facial dysmorphism. E (i) Schematic localisation of SDHD p.(Glu69Lys), p.(Asp92Gly) and p.(Ter160LeuextTer3) variants within the succinate dehydrogenase cytochrome b small subunit (CybS) domain of the SDHD polypeptide. The orange rectangle denotes the transit peptide (TP) domain, the red circle denotes the iron (haem axial ligand) binding site shared with SDHC and the blue circle denotes the ubiquinone binding site shared with SDHB. (ii) Conservation of the SDHD p.(Glu69Lys), p.(Asp92Gly) and p.(Ter160LeuextTer3) variants across species. F Visual depiction of the two autozygous regions on chromosome 11 (shown in red) common to affected individuals V:2, V:4 and V:6 including the 2.37 Mb region containing 21 genes including SDHD.
See this image and copyright information in PMC

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