A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome

Yoshihito Kishita, Masaru Shimura, Masakazu Kohda, Masumi Akita, Atsuko Imai-Okazaki, Yukiko Yatsuka, Yoko Nakajima, Tetsuya Ito, Akira Ohtake, Kei Murayama, Yasushi Okazaki

研究成果: Article

抜粋

Background: Mitochondrial DNA depletion syndrome (MTDPS) is part of a group of mitochondrial diseases characterized by a reduction in mitochondrial DNA copy number. Most MTDPS is caused by mutations in genes that disrupt deoxyribonucleotide metabolism. Methods: We performed the whole-exome sequencing of a hepato-encephalopathy patient with MTDPS and functional analyses to determine the clinical significance of the identified variant. Results: Here, whole-exome sequencing of a patient presenting with hepato-encephalopathy and MTDPS identified a novel homozygous frameshift variant, c.13_29del (p.Trp6Profs*71) in MICOS13. MICOS13 (also known as QIL1, MIC13, or C19orf70) is a component of the MICOS complex, which plays crucial roles in the maintenance of cristae junctions at the mitochondrial inner membrane. We found loss of MICOS13 protein and fewer cristae structures in the mitochondria of fibroblasts derived from the patient. Stable expression of a wild-type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies. Conclusion: Our findings suggest that the novel c.13_29del (p.Trp6Profs*71) MICOS13 variant causes hepato-encephalopathy with MTDPS. We propose that MICOS13 is classified as the cause of MTDPS.

元の言語English
ジャーナルMolecular genetics & genomic medicine
DOI
出版物ステータスAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Kishita, Y., Shimura, M., Kohda, M., Akita, M., Imai-Okazaki, A., Yatsuka, Y., Nakajima, Y., Ito, T., Ohtake, A., Murayama, K., & Okazaki, Y. (受理済み/印刷中). A novel homozygous variant in MICOS13/QIL1 causes hepato-encephalopathy with mitochondrial DNA depletion syndrome. Molecular genetics & genomic medicine. https://doi.org/10.1002/mgg3.1427