MPV17-related mitochondrial DNA maintenance defect

• Verfasst von: El-Hattab, Ayman W. [VerfasserIn]
• Verfasst von: Staufner, Christian [VerfasserIn]
• Titel: MPV17-related mitochondrial DNA maintenance defect
• Titelzusatz: new cases and review of clinical, biochemical, and molecular aspects
• Verf.angabe: Ayman W. El‐Hattab, Julia Wang, Hongzheng Dai, Mohammed Almannai, Christian Staufner, Majid Alfadhel, Michael J. Gambello, Pankaj Prasun, Saleem Raza, Hernando J. Lyons, Manal Afqi, Mohammed A. M. Saleh, Eissa A. Faqeih, Hamad I. Alzaidan, Abduljabbar Alshenqiti, Leigh Anne Flore, Jozef Hertecant, Stephanie Sacharow, Deborah S. Barbouth, Kei Murayama, Amit A. Shah, Henry C. Lin, Lee-Jun C. Wong
• Jahr: 2018
• Umfang: 10 S.
• Fussnoten: First published: 27 December 2017 ; Gesehen am 28.11.2018
• Titel Quelle: Enthalten in: Human mutation
• Ort Quelle: New York, NY [u.a.] : Wiley-Liss, 1992
• Jahr Quelle: 2018
• Band/Heft Quelle: 39(2018), 4, Seite 461-470
• ISSN Quelle: 1098-1004
• DOI: doi:10.1002/humu.23387
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: mitochondrial DNA (mtDNA)
• Sach-SW: MPV17
• Sach-SW: mtDNA depletion
• Sach-SW: mtDNA maintenance
• Sach-SW: multiple mtDNA deletions
• K10plus-PPN: 1584578610

Abstract

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.