The MPV17 gene gives instructions for making a mitochondrial inner membrane protein that is involved in mitochondrial homeostasis. The function of MPV17 is still unknown; it may be involved in the metabolism of reactive oxygen species and control of oxidative phosphorylation and mitochondrial DNA (mtDNA) maintenance.
Defects in this protein have been associated with MPV17-related hepatocerebral form of mitochondrial DNA depletion syndrome, characterized by severe liver failure, hypoglycemia, growth retardation, neurological symptoms, and multiple brain lesions during the first year of life.
The MPV17 gene is located on 2p23.3 chromosome; it has 7 coding exons and spans approximately 16.2 kb in the genomic DNA. It encodes a protein of 176 amino acids. More than 30 mutations in this gene including: missense, nonsense, splicing site mutations, and small deletion/insertions have been found to cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Also, a large intragenic deletion spanning exon 8 of MPV17 has been reported.
AlSaman et al. (2012) reported a Saudi boy born to first cousin parents with hepatocerebral form of Mitochondrial DNA depletion syndromes (MDSs), who was admitted on the second day of birth because of poor feeding, vomiting, and episodes of hypoglycemia. The 7 coding exons and the exon-intron boundaries of the MPV17 gene were amplified from patient’s DNA extracted from muscle and directly sequenced. A homozygous (IVS3 G>T) transversion mutation was identified in intron 3. This mutation destroys the donor splice site of exon 2, resulting in aberrant mRNA and protein.
Sarkhy et al. (2014) described a Saudi infant with hepatocerebral MDS. MPV17 sequencing revealed the presence of a novel homozygous variant, c.278A>C (p.Q93P). This mutation was predicted to cause the substitution of a highly conserved amino acid.
Al-Hussaini identified pathogenic variants in the MPV17 gene in seven patients with suspected hepatocerebral MDS in Saudi Arabia. Three of these were novel mutations.