Journal article
Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene
Human mutation, Vol.38(5), pp.511-516
05/2017
DOI: 10.1002/humu.23196
PMID: 28185376
Abstract
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.
Details
- Title: Subtitle
- Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene
- Creators
- Kristin D Kernohan - Children's Hospital of Eastern OntarioDavid A Dyment - Children's Hospital of Eastern OntarioMihaela Pupavac - McGill UniversityZvi Cramer - McGill UniversityArran McBride - Children's Hospital of Eastern OntarioGenevieve Bernard - McGill UniversityIsabella Straub - McGill UniversityMartine Tetreault - McGill University and Génome Québec Innovation CentreTaila Hartley - Children's Hospital of Eastern OntarioLijia Huang - Children's Hospital of Eastern OntarioErick Sell - Children's Hospital of Eastern OntarioJacek Majewski - McGill UniversityDavid S Rosenblatt - McGill UniversityEric Shoubridge - McGill UniversityAziz Mhanni - University of ManitobaTara Myers - Mercy HospitalVirginia Proud - Children's Hospital of The King's DaughtersSamanta Vergano - Children's Hospital of The King's DaughtersBrooke Spangler - Children's Hospital of The King's DaughtersEmily Farrow - Children's Mercy HospitalJennifer Kussman - Mercy HospitalNicole Safina - Mercy HospitalCarol Saunders - Children's Mercy HospitalKym M Boycott - Children's Hospital of Eastern OntarioIsabelle Thiffault - Children's Mercy HospitalCare4Rare Consortium
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.38(5), pp.511-516
- DOI
- 10.1002/humu.23196
- PMID
- 28185376
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Grant note
- CIHR
- Language
- English
- Date published
- 05/2017
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354038902771
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