Effectiveness of whole exome sequencing in unsolved patients with a clinical suspicion of a mitochondrial disorder in Estonia

Molecular Genetics and Metabolism Reports
Sanna PuuseppKatrin Õunap

Abstract

Reaching a genetic diagnosis of mitochondrial disorders (MDs) is challenging due to their broad phenotypic and genotypic heterogeneity. However, there is growing evidence that the use of whole exome sequencing (WES) for diagnosing patients with a clinical suspicion of an MD is effective (39-60%). We aimed to study the effectiveness of WES in clinical practice in Estonia, in patients with an unsolved, but suspected MD. We also show our first results of mtDNA analysis obtained from standard WES reads. Retrospective cases were selected from a database of 181 patients whose fibroblast cell cultures had been stored from 2003 to 2013. Prospective cases were selected during the period of 2014-2016 from patients referred to a clinical geneticist in whom an MD was suspected. We scored each patient according to the mitochondrial disease criteria (MDC) (Morava et al., 2006) after re-evaluation of their clinical data, and then performed WES analysis. A total of 28 patients were selected to the study group. A disease-causing variant was found in 16 patients (57%) using WES. An MD was diagnosed in four patients (14%), with variants in the SLC25A4, POLG, SPATA5, and NDUFB11 genes. Other variants found were associated with a neuromuscular dise...Continue Reading

Citations

Apr 22, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lisa G RileyJohn Christodoulou
Nov 7, 2019·Journal of Clinical Medicine·Irene Bravo-AlonsoPilar Rodríguez-Pombo
May 22, 2019·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Takayuki FujiiJun-Ichi Kira
Oct 31, 2020·EMBO Molecular Medicine·Karit Reinson, Katrin Õunap
Sep 24, 2020·The Journal of Pediatrics·Audrey C Woerner, Jerry Vockley
Mar 4, 2021·FEBS Letters·Mirjana Gusic, Holger Prokisch
Feb 5, 2021·The Journal of Clinical Investigation·Niccolò E MencacciClaudio Acuna
May 1, 2021·Diagnostics·Andrea BarpValeria Ada Sansone
Aug 8, 2021·International Journal of Molecular Sciences·Frederik BraunUlrike Schara-Schmidt
Nov 5, 2021·BMJ : British Medical Journal·Katherine R SchonUNKNOWN Genomics England Research Consortium
Nov 24, 2020·Archives of Biochemistry and Biophysics·V MontanoM Mancuso

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Methods Mentioned

BETA
exome sequencing
biopsy
electron microscopy
nucleotide
GTPase
SMA
biopsies

Software Mentioned

PolyPhen
GATK
MutationTaster
BWA MEM
GATK DepthOfCoverage
Annovar
Burrows Aligner ( BWA )
mpileup
SIFT
Genome Analysis Toolkit ( GATK )

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