HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Molecular genetic testing for mitochondrial disease: from one generation to the next.

Abstract
Molecular genetic diagnostic testing for mitochondrial disease has evolved continually since the first genetic basis for a clinical mitochondrial disease syndrome was identified in the late 1980s. Owing to global limitations in both knowledge and technology, few individuals, even among those with strong clinical or biochemical evidence of mitochondrial respiratory chain dysfunction, ever received a definitive molecular diagnosis prior to 2005. Clinically available genetic diagnostic testing options improved by 2006 to include sequencing and deletion analysis of an increasing number of individual nuclear genes linked to mitochondrial disease, genome-wide microarray analysis for chromosomal copy number abnormalities, and mitochondrial DNA whole genome sequence analysis. To assess the collective effect of these tests on the genetic diagnosis of suspected mitochondrial disease, we report here results from a retrospective review of the diagnostic yield in patients evaluated from 2008 to 2011 in the Mitochondrial-Genetics Diagnostic Clinic at The Children's Hospital of Philadelphia. Among 152 patients aged 6 weeks to 81 years referred for clinical evaluation of multisystem presentations concerning for suspected mitochondrial disease, a genetic etiology was established that confirmed definite mitochondrial disease in 16.4% and excluded primary mitochondrial disease in 9.2%. Substantial diagnostic challenges remain owing to the clinical difficulty and frank low yield of a priori selecting individual nuclear genes to sequence based on particular symptomatic or biochemical manifestations of suspected mitochondrial disease. These findings highlight the particular utility of massively parallel nuclear exome sequencing technologies, whose benefits and limitations are explored relative to the clinical genetic diagnostic evaluation of mitochondrial disease.
AuthorsElizabeth McCormick, Emily Place, Marni J Falk
JournalNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 10 Issue 2 Pg. 251-61 (Apr 2013) ISSN: 1878-7479 [Electronic] United States
PMID23269497 (Publication Type: Historical Article, Journal Article, Research Support, N.I.H., Extramural, Review)
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Exome (genetics)
  • Genetic Testing (history, trends)
  • Genome, Human (genetics)
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Infant
  • Middle Aged
  • Mitochondrial Diseases (diagnosis, genetics)
  • Sequence Analysis, DNA (trends)
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: