A novel RRM2B mutation associated with mitochondrial DNA depletion syndrome

Monica Fumagalli; Dario Ronchi; Maria Francesca Bedeschi; Arianna Manini; Gloria Cristofori; Fabio Mosca; Robertino Dilena; Monica Sciacco; Simona Zanotti; Daniela Piga; Gianluigi Ardissino; Fabio Triulzi; Stefania Corti; Giacomo P Comi; Leonardo Salviati

doi:10.1016/j.ymgmr.2022.100887

A novel RRM2B mutation associated with mitochondrial DNA depletion syndrome

Mol Genet Metab Rep. 2022 Jun 18:32:100887. doi: 10.1016/j.ymgmr.2022.100887. eCollection 2022 Sep.

Authors

Monica Fumagalli^{1

2}, Dario Ronchi³, Maria Francesca Bedeschi⁴, Arianna Manini³, Gloria Cristofori¹, Fabio Mosca^{1

2}, Robertino Dilena⁵, Monica Sciacco⁶, Simona Zanotti⁶, Daniela Piga⁷, Gianluigi Ardissino⁸, Fabio Triulzi^{3

9}, Stefania Corti^{3

7}, Giacomo P Comi^{3

6}, Leonardo Salviati^{10

11}

Affiliations

¹ Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy.
² University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy.
³ Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
⁴ Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOD Medical Genetics, Milan, Italy.
⁵ Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Neurophysiology,Milan, Italy.
⁶ Fondazione IRCCS CCà Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, Italy.
⁷ Fondazione IRCCS CCà Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy.
⁸ Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Nefrologia, Dialisi E Trapianto Pediatrico, Milan, Italy.
⁹ Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Unit of Neuroradiology, Milan, Italy.
¹⁰ Clinical Genetics Unit, Department of Women's and Children's Health, and Myology Center, University of Padova, Padova, Italy.
¹¹ IRP Città della Speranza, Padova, Italy.

Abstract

Mitochondrial DNA (mtDNA) depletion syndromes are disorders characterized by infantile-onset, severe progression, and the drastic loss of mtDNA content in affected tissues. In a patient who showed severe hypotonia, proximal tubulopathy and sensorineural hearing loss after birth, we observed severe mtDNA depletion and impaired respiratory chain activity in muscle due to heterozygous variants c.686G > T and c.551-2A > G in RRM2B, encoding the p53R2 subunit of the ribonucleotide reductase.

Keywords: Mitochondrial DNA depletion; Mitochondrial encephalomyopathy; Next generation sequencing; RRM2B; Ribonucleotide reductase.

Publication types

Case Reports