A novel homozygous variant in MICOS13/QIL1 causes hepato‐encephalopathy with mitochondrial DNA depletion syndrome. Issue 10 (4th August 2020)

• Record Type: Journal Article
• Authors: Kishita, Yoshihito; Shimura, Masaru; Kohda, Masakazu; Akita, Masumi; Imai‐Okazaki, Atsuko; Yatsuka, Yukiko; Nakajima, Yoko; Ito, Tetsuya; Ohtake, Akira; Murayama, Kei; Okazaki, Yasushi
• Is Part Of: Molecular genetics & genomic medicine. Volume 8:Issue 10(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-04
• Subjects: cristae -- MICOS complex -- mitochondrial disease -- mitochondrial DNA depletion syndrome; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1427
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : We performed the whole‐exome sequencing of the hepato‐encephalopathy patient with MTDPS. The functional analyses revealed the clinical significance of the identified variant.