Details

Autor(en) / Beteiligte

• Shepheard, Stephanie R
• Parker, Matthew D
• Cooper-Knock, Johnathan
• Verber, Nick S
• Tuddenham, Lee
• Heath, Paul
• Beauchamp, Nick
• Place, Elsie
• Sollars, Elizabeth S A
• Turner, Martin R
• Malaspina, Andrea
• Fratta, Pietro
• Hewamadduma, Channa
• Jenkins, Thomas M
• McDermott, Christopher J
• Wang, Dennis
• Kirby, Janine
• Shaw, Pamela J

Titel

Value of systematic genetic screening of patients with amyotrophic lateral sclerosis

Ist Teil von

• Journal of neurology, neurosurgery and psychiatry, 2021-05, Vol.92 (5), p.510

Ort / Verlag

England

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care. We performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases. 21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074). Routine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients.