Large‐scale mitochondrial DNA deletion underlying familial multiple system atrophy of the cerebellar subtype

Abstract

Key Clinical MessageA family with mitochondrial inheritance of multiple system atrophy of the cerebellar subtype. MRI brain shows significant cerebellar atrophy with mild pontine atrophy and the classical hot cross bun sign in Pons. The muscle biopsy was indicative of mitochondrial myopathy. Mitochondrial DNA analysis revealed a low‐level large mtDNA deletion, m.3264_1607del12806 bp.

Genetic and clinical features of Chinese patients with mitochondrial ataxia identified by targeted next‐generation sequencing

“…The mtDNA depletion, reduction in cellular mtDNA copy number, is characterized in mtDNA depletion syndromes (MDDSs), a genetically and clinically heterogeneous group of disorders caused by molecular defects in at least 9 nuclear genes involved in mtDNA biosynthesis and the maintenance of the deoxynucleotide (dNTP) pools . Although rare, ataxia has been reported in patients with large‐scale mitochondrial DNA deletions or mtDNA depletion syndromes caused by mutations in POLG , C10orf2, and TYMP genes . Mitochondrial DNA deletion/depletion load varies widely among different tissues, and there will be a challenge for molecular analysis if mutations manifest mainly or solely in a specific organ.…”

“…43 Although rare, ataxia has been reported in patients with large-scale mitochondrial DNA deletions or mtDNA depletion syndromes caused by mutations in POLG, C10orf2, and TYMP genes. [44][45][46] Mitochondrial DNA deletion/depletion load varies widely among different tissues, and there will be a challenge for molecular analysis if mutations manifest mainly or solely in a specific organ. In generally, DNA from urinary sediment and skeletal muscle had the higher proportion of mutant genomes than blood, which has been proven not sensitive for detecting mtDNA depletion.…”

Cerebral imaging in paediatric mitochondrial disorders

“…150 Single mtDNA deletions may manifest as MIMODS with onset from infancy to adulthood. 151 Cerebral imaging in these patients may reveal a hot-cross bun sign, thus mimicking multiple system atrophy of the cerebellar subtype. 151…”

“…151 Cerebral imaging in these patients may reveal a hot-cross bun sign, thus mimicking multiple system atrophy of the cerebellar subtype. 151…”

Cerebral Manifestations of Mitochondrial Disorders

“…Predominantly cortical atrophy has been reported in patients with CPEO 130 . Pontine and cerebellar atrophy with a hot cross bun sign resulting from the mtDNA deletion m.3264_1607del12806 may clinically mimic the cerebellar type of multisystem atrophy (MSA-C) manifesting as dysarthria, nystagmus, falls, tremor, impaired coordination, incontinence, dysphagia, or frequent choking 131 …”