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Open Access 01-12-2021 | Diseases of the neuromuscular synapses and muscles | Case Study

Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family

Authors: Fatemeh Bitarafan, Mehrnoosh Khodaeian, Elham Amjadi Sardehaei, Fatemeh Zahra Darvishi, Navid Almadani, Yalda Nilipour, Masoud Garshasbi

Published in: Molecular and Cellular Pediatrics | Issue 1/2021

Abstract

Background

Ca²⁺ as a universal second messenger regulates basic biological functions including cell cycle, cell proliferation, cell differentiation, and cell death. Lack of the protein mitochondrial calcium uptake1 (MICU1), which has been regarded as a gatekeeper of Ca ions, leads to the abnormal mitochondrial Ca²⁺ handling, excessive production of reactive oxygen species (ROS), and increased cell death. Mutations in MICU1 gene causes a very rare neuromuscular disease, myopathy with extrapyramidal signs (MPXPS), due to primary alterations in mitochondrial calcium signaling which demonstrates the key role of mitochondrial Ca²⁺ uptake. To date, 13 variants have been reported in MICU1 gene in 44 patients presented with the vast spectrum of symptoms.

Case presentation

Here, we report a 44-year-old Iranian patient presented with learning disability, muscle weakness, easy fatigability, reduced tendon reflexes, ataxia, gait disturbance, elevated hepatic transaminases, elevated serum creatine kinase (CK), and elevated lactate dehydrogenase (LDH). We identified a novel nonsense variant c.385C>T; p.(R129*) in MICU1 gene by whole exome sequencing (WES) and segregation analysis.

Conclusions

Our finding along with previous studies provides more evidence on the clinical presentation of the disease caused by pathogenic mutations in MICU1. Finding more variants and expanding the spectrum of the disease increases the diagnostic rate of molecular testing in screening of this kind of diseases and in turn improves the quality of counseling for at risk couples and helps them to minimize the risks of having affected children.

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Title: Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family
Authors: Fatemeh Bitarafan
Mehrnoosh Khodaeian
Elham Amjadi Sardehaei
Fatemeh Zahra Darvishi
Navid Almadani
Yalda Nilipour
Masoud Garshasbi
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Diseases of the neuromuscular synapses and muscles
Myopathy
Published in: Molecular and Cellular Pediatrics / Issue 1/2021
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-021-00116-w

At a glance: The STEP trials

Springer Medicine

Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family

Abstract

Background

Case presentation

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Case presentation

Conclusions

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