期刊
HUMAN MUTATION
卷 38, 期 5, 页码 511-516出版社
WILEY
DOI: 10.1002/humu.23196
关键词
TRIT1; developmental disorders; epilepsy; brain anomalies; intellectual disability; tRNA
资金
- Marion Merrell Dow Foundation
- Children's Mercy - Kansas City
- W.T. Kemper Foundation
- Pat & Gil Clements Foundation
- Claire Giannini Foundation
- Black Veatch
- Genome Canada
- Canadian Institutes of Health Research
- Ontario Genomics Institute
- Ontario Research Fund
- Genome Quebec
- Children's Hospital of Eastern Ontario Foundation
- Patton Trust
Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease-gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created matching platforms. We describe four individuals from three unrelated families matched by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease-causing gene and interprets the variants as pathogenic. TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.
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