Wellcome Trust Centre For Mitochondrial Research

Dr Charlotte Alston

Personal Biography

Charlotte-Alston

Mitochondrial diseases are common genetic disorders caused by defective energy production. They affect numerous organs and due to the clinical and genetic heterogeneity, obtaining a genetic diagnosis is often difficult yet crucial for the counselling of patients and their families. There are no cures but establishing a genetic diagnosis enables patients and their families’ access to genetic and reproductive counselling.

I am a State Registered Clinical Scientist and have spent the last 12 years working in the Nationally-Commissioned mitochondrial diagnostic laboratory in Newcastle. Our current testing strategy relies upon functional analysis of a muscle biopsy and selective candidate gene sequencing; whilst this strategy establishes a genetic diagnosis for many patients, approximately half our patients remain without a genetic diagnosis.

I am particularly interested in paediatric mitochondrial disease, and spent much of my PhD improving the genetic diagnosis pathway for paediatric patients with mitochondrial disease through implementation of next-generation sequencing (NGS) technologies within a diagnostic setting.

For families who have lost a child, establishing a genetic diagnosis means that we can offer reproductive options to Mum and Dad, such as prenatal testing by either chorionic villus biopsy or amniocentesis, enables us to determine – from as early as 10 weeks of gestation – whether their subsequent pregnancies have inherited the same gene mutations.

Research Project

Is muscle biopsy necessary for the diagnosis of paediatric mitochondrial disease? 

Principal Investigators: Professor Rob Taylor and Professor Robert McFarland

Project Details

Mitochondrial diseases are common genetic disorders caused by defective energy production. They affect numerous organs and due to the clinical and genetic heterogeneity, obtaining a genetic diagnosis is often difficult yet crucial for the counselling of patients and their families. There are no cures but establishing a genetic diagnosis enables patients and their families’ access to genetic and reproductive counselling.

I am a HCPC Registered Clinical Scientist and have spent the last 12 years working in the Nationally-Commissioned mitochondrial diagnostic laboratory in Newcastle. Our multidisciplinary service uses histochemical and biochemical assessment of mitochondrial respiratory chain activities, together with molecular genetic analysis of nuclear-encoded and mitochondrial-encoded disease genes to provide a genetic diagnosis for mitochondrial disease patients;  whilst this strategy establishes a genetic diagnosis for many patients, many remain without a genetic diagnosis using our existing strategies.

I completed my NIHR funded PhD in 2017, and my research focused upon improving the diagnostic yield and speed for paediatric patients with complex 1 deficiency. My research was adopted by the diagnostic service, but clearly complex 1 deficiency is but one subtype of mitochondrial disease and requires a muscle biopsy. I recently commenced a NIHR Post doctoral fellowship with a view to building on my PhD research. This time I hope to demonstrate that muscle biopsy is not required, and trio whole exome sequencing will yield the best possible diagnostic results. Variants of uncertain pathological significance (VUS) are often identified in patients with no clear genetic diagnosis and evolving molecular biology tools, such as CRISPR /Cas9 gene editing, could clearly show them as benign or the cause of disease – this is currently beyond NHS scope but I will develop a pipeline to bring this cutting edge technology into the diagnostic arena to improve the counseling of families affected by mitochondrial disease, both within the NHS and further afield.

Sponsor/funder: National Institute for Health Research (NIHR)

Publications: https://www.ncl.ac.uk/ion/staff/profile/charlottealston.html#publications

Contact: charlotte.alston@ncl.ac.uk