Genetic Testing for Mitochondrial Disorders Part 2

Question 1

Outline the genetic diagnosis of autosomal disorders of mtDNA maintenance in the UK.

Answer 1

In the UK, a diagnostic service for mtDNA maintenance disorders is provided as part of the NHS Highly Specialised Service funded Rare Mitochondrial Disorders Service for Adults and Children (centres in Oxford, London and Newcastle).

This comprises 2 components:

1) . Analysis of the secondary mtDNA defects:
- Analysis for mtDNA depletion in muscle or liver.
- Analysis for multiple mtDNA deletions in muscle.

2) . Analysis of the primary nuclear defects:
- Any DNA sample is suitable.
- Sequencing (and dosage analysis) of nuclear genes known to cause disorders of mtDNA maintenance.
- Current approach in the UK is to use panels by Sanger sequencing.
- In development is the use of targeted NGS to analyse a larger panel of genes associated with mtDNA maintenance disorders in a single assay.

Question 2

What test is typically utilised to look for mitochondrial depletion in the liver?

Answer 2

Quantitative real-time PCR - amplify mtDNA and compare it to amplification of nuclear DNA.