MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions

Area of Science:

• Genetics and Molecular Biology
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial DNA (mtDNA) deletions are associated with various multisystemic disorders.
• The genetic causes of adult-onset mitochondrial diseases with multiple mtDNA deletions are not fully understood.

Purpose of the Study:

• To identify the underlying genetic cause of an adult-onset multisystemic disease characterized by multiple mtDNA deletions.

Main Methods:

• Case report of a 65-year-old male patient presenting with diverse symptoms.
• Analysis of skeletal muscle biopsy for mitochondrial abnormalities (ragged-red fibers, cytochrome-c oxidase deficiency).
• Molecular genetic testing including Southern blot, quantitative polymerase chain reaction, and exome sequencing with a mitochondrial library.

Main Results:

• Skeletal muscle biopsy confirmed mitochondrial abnormalities and multiple mtDNA deletions.
• Exome sequencing identified compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*) as the cause.
• No mtDNA deletions were found in fibroblasts, and mtDNA quantity was normal in both tissues.

Conclusions:

• MPV17 mutations are a novel cause of adult-onset multisystemic disease with multiple mtDNA deletions.
• This expands the clinical spectrum of MPV17-related disorders, previously associated mainly with juvenile-onset mtDNA depletion syndromes.