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

• Published in: Molecular and cellular pediatrics Vol. 8; no. 1; p. 6
• Main Authors: Bitarafan, Fatemeh, Khodaeian, Mehrnoosh, Amjadi Sardehaei, Elham, Darvishi, Fatemeh Zahra, Almadani, Navid, Nilipour, Yalda, Garshasbi, Masoud
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 09.05.2021; Springer Nature B.V
• Subjects: Apoptosis; Ataxia; Calcium (mitochondrial); Calcium influx; Calcium signalling; Case Study; Cell cycle; Cell death; Cell differentiation; Cell proliferation; Creatine; Creatine kinase; Diabetes; Disease; Endocrinology; Extrapyramidal system; Gait; Kinases; L-Lactate dehydrogenase; Lactic acid; Medicine; Medicine & Public Health; Mitochondria; Movement disorders; Mutation; Myopathy; Neuromuscular diseases; Oncology; Pediatrics; Reactive oxygen species; Reflexes; Mitochondrial calcium uptake 1 (MICU1); Ca; Myopathy with extrapyramidal signs (MPXPS); Whole exome sequencing (WES); Ca2
• DOI: 10.1186/s40348-021-00116-w
• ISSN: 2194-7791

Background Ca 2+ 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 Ca 2+ 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 Ca 2+ 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.