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

Molecular and Cellular Pediatrics

Fatemeh Bitarafan¹  Navid Almadani²  Elham Amjadi Sardehaei³  Fatemeh Zahra Darvishi³  Mehrnoosh Khodaeian³  Masoud Garshasbi⁴  Yalda Nilipour⁵ 

[1] Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran;Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;Department of Medical Genetics, DeNA Laboratory, Tehran, Iran;Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran;

关键词: Ca;    Mitochondrial calcium uptake 1 (MICU1);    Myopathy with extrapyramidal signs (MPXPS);    Whole exome sequencing (WES);   

DOI  :  10.1186/s40348-021-00116-w

来源: Springer

【 摘 要 】

BackgroundCa2+ 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 presentationHere, 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.ConclusionsOur 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.

【 授权许可】

CC BY