RRC ID 36260
Author Kohda M, Tokuzawa Y, Kishita Y, Nyuzuki H, Moriyama Y, Mizuno Y, Hirata T, Yatsuka Y, Yamashita-Sugahara Y, Nakachi Y, Kato H, Okuda A, Tamaru S, Borna NN, Banshoya K, Aigaki T, Sato-Miyata Y, Ohnuma K, Suzuki T, Nagao A, Maehata H, Matsuda F, Higasa K, Nagasaki M, Yasuda J, Yamamoto M, Fushimi T, Shimura M, Kaiho-Ichimoto K, Harashima H, Yamazaki T, Mori M, Murayama K, Ohtake A, Okazaki Y.
Title A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.
Journal PLoS Genet.
Abstract Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4) as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3) and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21) as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.
Volume 12(1)
Pages e1005679
Published 2016-1
DOI 10.1371/journal.pgen.1005679
PII PGENETICS-D-15-01978
PMID 26741492
PMC PMC4704781
MeSH Adolescent Child Child, Preschool Chromosome Aberrations DNA, Mitochondrial / genetics Exome / genetics* Female Fibroblasts Genetic Heterogeneity* High-Throughput Nucleotide Sequencing Humans INDEL Mutation / genetics Infant Infant, Newborn Male Mitochondria / genetics* Mitochondria / pathology Mitochondrial Diseases / diagnosis Mitochondrial Diseases / genetics* Mitochondrial Diseases / pathology Polymorphism, Single Nucleotide / genetics
IF 5.54
Times Cited 11
WOS Category GENETICS & HEREDITY
Resource
Drosophila GFP-IR-2