TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

Dario Ronchi; Leonardo Caporali; Giulia Francesca Manenti; Megi Meneri; Susan Mohamed; Andreina Bordoni; Francesca Tagliavini; Manuela Contin; Daniela Piga; Monica Sciacco; Cristina Saetti; Valerio Carelli; Giacomo Pietro Comi

doi:10.3389/fgene.2020.00860

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

Dario Ronchi, Leonardo Caporali, Giulia Francesca Manenti, Megi Meneri, Susan Mohamed, Andreina Bordoni, Francesca Tagliavini, Manuela Contin, Daniela Piga, Monica Sciacco, Cristina Saetti, Valerio Carelli, Giacomo Pietro Comi

Research output: Contribution to journal › Article › peer-review

Abstract

Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.

Original language	English
Article number	860
Journal	Frontiers in Genetics
Volume	11
DOIs	https://doi.org/10.3389/fgene.2020.00860
Publication status	Published - Aug 5 2020

Keywords

mitochondrial DNA instability
mitochondrial DNA replication
mitochondrial myopathy
mitochondrial neurogatrointestinal encephalomyopathy
TYMP

ASJC Scopus subject areas

Molecular Medicine
Genetics
Genetics(clinical)

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10.3389/fgene.2020.00860

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title = "TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis",

abstract = "Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.",

keywords = "mitochondrial DNA instability, mitochondrial DNA replication, mitochondrial myopathy, mitochondrial neurogatrointestinal encephalomyopathy, TYMP",

author = "Dario Ronchi and Leonardo Caporali and Manenti, {Giulia Francesca} and Megi Meneri and Susan Mohamed and Andreina Bordoni and Francesca Tagliavini and Manuela Contin and Daniela Piga and Monica Sciacco and Cristina Saetti and Valerio Carelli and Comi, {Giacomo Pietro}",

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day = "5",

doi = "10.3389/fgene.2020.00860",

language = "English",

volume = "11",

journal = "Frontiers in Genetics",

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TY - JOUR

T1 - TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

AU - Ronchi, Dario

AU - Caporali, Leonardo

AU - Manenti, Giulia Francesca

AU - Meneri, Megi

AU - Mohamed, Susan

AU - Bordoni, Andreina

AU - Tagliavini, Francesca

AU - Contin, Manuela

AU - Piga, Daniela

AU - Sciacco, Monica

AU - Saetti, Cristina

AU - Carelli, Valerio

AU - Comi, Giacomo Pietro

PY - 2020/8/5

Y1 - 2020/8/5

N2 - Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.

AB - Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.

KW - mitochondrial DNA instability

KW - mitochondrial DNA replication

KW - mitochondrial myopathy

KW - mitochondrial neurogatrointestinal encephalomyopathy

KW - TYMP

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DO - 10.3389/fgene.2020.00860

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JO - Frontiers in Genetics

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SN - 1664-8021

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TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

Abstract

Keywords

ASJC Scopus subject areas

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