Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy

Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy Publisher Pubmed

Heidari E¹ ; Rasoulinezhad M² ; Pak N³ ; Reza Ashrafi M² ; Heidari M² ; Banwell B⁴ ; Garshasbi M¹ ; Reza Tavasoli A²

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1. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2. Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
3. Pediatric Radiology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
4. Division of Child Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Source: Mitochondrion Published:2021

Abstract

Complex III (CIII) is the third out of five mitochondrial respiratory chain complexes residing at the mitochondrial inner membrane. The assembly of 10 subunits encoded by nuclear DNA and one by mitochondrial DNA result in the functional CIII which transfers electrons from ubiquinol to cytochrome c. Deficiencies of CIII are among the least investigated mitochondrial disorders and thus clinical spectrum of patients with mutations in CIII is not well defined. We report on a 10-year-old girl born to consanguineous Iranian parents presenting with recurrent visual loss episodes and optic nerve contrast enhancement in brain imaging reminiscent of an acquired demyelination syndrome (i.e. optic neuritis or multiple sclerosis), who was ultimately confirmed to have a novel homozygous missense variant of unknown significance, c.949C > T; p.(Arg317Trp) in the CYC1 gene, a nuclear DNA subunit of complex III of the mitochondrial chain. Sanger sequencing confirmed the segregation of this variant with disease in the family. The effect of this variant on the protein structure was shown in-silico. Our findings, not only expand the clinical spectrum due to defects in CYC1 gene but also highlight that mitochondrial respiratory chain disorders could be considered as a potential differential diagnosis in children who present with unusual patterns of acquired demyelination syndromes (ADS). In addition, our results support the hypothesis that mitochondrial disorders might have an overlapping presentation with ADS. © 2021 Elsevier B.V. and Mitochondria Research Society

2. An Update on Clinical, Pathological, Diagnostic, and Therapeutic Perspectives of Childhood Leukodystrophies, Expert Review of Neurotherapeutics (2020)

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Mahmoudreza Ashrafi (3)

Ali Reza Tavasoli (3)

Style	Citing Format
MLA	Heidari E, et al.. "Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy." Mitochondrion, vol. 60, no. , 2021, pp. 12-20.
APA	Heidari E, Rasoulinezhad M, Pak N, Reza Ashrafi M, Heidari M, Banwell B, Garshasbi M, Reza Tavasoli A (2021). Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy. Mitochondrion, 60(), 12-20.
Chicago	Heidari E, Rasoulinezhad M, Pak N, Reza Ashrafi M, Heidari M, Banwell B, Garshasbi M, Reza Tavasoli A. "Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy." Mitochondrion 60, no. (2021): 12-20.
Harvard	Heidari E et al. (2021) 'Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy', Mitochondrion, 60(), pp. 12-20.
Vancouver	Heidari E, Rasoulinezhad M, Pak N, Reza Ashrafi M, Heidari M, Banwell B, et al.. Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy. Mitochondrion. 2021;60():12-20.
BibTex	@article{ author = {Heidari E and Rasoulinezhad M and Pak N and Reza Ashrafi M and Heidari M and Banwell B and Garshasbi M and Reza Tavasoli A}, title = {Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy}, journal = {Mitochondrion}, volume = {60}, number = {}, pages = {12-20}, year = {2021} }
RIS	TY - JOUR AU - Heidari E AU - Rasoulinezhad M AU - Pak N AU - Reza Ashrafi M AU - Heidari M AU - Banwell B AU - Garshasbi M AU - Reza Tavasoli A TI - Defective Complex Iii Mitochondrial Respiratory Chain Due to a Novel Variant in Cyc1 Gene Masquerades Acute Demyelinating Syndrome or Leber Hereditary Optic Neuropathy JO - Mitochondrion VL - 60 IS - SP - 12 EP - 20 PY - 2021 ER -

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