Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience.

Annals of Clinical and Translational Neurology
Sarah J BeecroftNigel G Laing

Abstract

To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in a national referral center. We designed two iterations of a comprehensive targeted gene panel for neuromuscular disorders. Version 1 included 336 genes, which was increased to 464 genes in Version 2. Both panels used TargetSeqTM probe-based hybridization for target enrichment followed by Ion Torrent sequencing. Targeted high-coverage sequencing and analysis was performed on 2249 neurology patients from Australia and New Zealand (1054 Version 1, 1195 Version 2) from 2012 to 2015. No selection criteria were used other than referral from a suitable medical specialist (e.g., neurologist or clinical geneticist). Patients were classified into 15 clinical categories based on the clinical diagnosis from the referring clinician. Six hundred and sixty-five patients received a genetic diagnosis (30%). Diagnosed patients were significantly younger that undiagnosed patients (26.4 and 32.5 years, respectively; P = 4.6326E-9). The diagnostic success varied markedly between disease categories. Pathogenic variants in 10 genes explained 38% of the disease burden. Unexpected phenotypic expansions were discovered in multiple cases. Triage of unsolved cases for resea...Continue Reading

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Citations

Aug 28, 2020·Brain : a Journal of Neurology·Sarah J BeecroftRichard H Roxburgh
Sep 9, 2020·Neuropathology and Applied Neurobiology·L González-MeraM Olivé
May 1, 2021·Diagnostics·Andrea BarpValeria Ada Sansone
Jun 25, 2021·Neuropathology and Applied Neurobiology·Edoardo MalfattiGianina Ravenscroft

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Methods Mentioned

BETA
chip
exome sequencing

Software Mentioned

Torrent Suite
GraphPad
ANNOVAR
Cartagenia BenchLab
GraphPad Prism
SPSS Statistics

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