Establishment and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene

Elizabeth H Jacobs; Jacquelyn Schatzman Raposo; Annarita Scardamaglia; Fowzan S Alkuraya; Shahriar Nafissi; Henry Houlden; Stephan Zuchner; Mario A Saporta

doi:10.1016/j.scr.2024.103599

Establishment and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene

Stem Cell Res. 2024 Dec:81:103599. doi: 10.1016/j.scr.2024.103599. Epub 2024 Oct 22.

Authors

Elizabeth H Jacobs¹, Jacquelyn Schatzman Raposo², Annarita Scardamaglia³, Fowzan S Alkuraya⁴, Shahriar Nafissi⁵, Henry Houlden³, Stephan Zuchner², Mario A Saporta⁶

Affiliations

¹ Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL, USA.
² Hussmann Institute for Human Genetics and Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
³ Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, London, United Kingdom.
⁴ Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁵ Iranian Neuromuscular Research Center, Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: [email protected].

PMID: 39461113
DOI: 10.1016/j.scr.2024.103599

Abstract

Myotubularin-Related Protein 5 (MTMR5) is an inactive, poorly characterized D3-phosphatidylinositol phosphatase. Mutations in MTMR5 have been linked to Charcot-Marie-Tooth Disease Type 4B3 (CMT4B3), a rare, early-onset, recessive peripheral neuropathy. Here, we describe the establishment and validation of three human induced pluripotent stem cell (iPSC) lines derived from unrelated CMT4B3 patients, each harboring homozygous MTMR5/Sbf1 mutations. Current MTMR5 ^-/- animal models do not clearly link Sbf1 mutations to severe neuropathy, so such a resource is highly desired to further elucidate the relationship between MTMR5 dysfunction and peripheral nerve degeneration.

MeSH terms

Cell Line
Charcot-Marie-Tooth Disease* / genetics
Charcot-Marie-Tooth Disease* / pathology
Female
Humans
Induced Pluripotent Stem Cells* / metabolism
Male
Mutation*
Protein Tyrosine Phosphatases, Non-Receptor / genetics
Protein Tyrosine Phosphatases, Non-Receptor / metabolism

Substances

Protein Tyrosine Phosphatases, Non-Receptor