Whole Genome Sequencing-Based Diagnosis of Spinocerebellar Ataxia Type 3 Repeat Expansion Neuromuscular Disorders in an Undiagnosed Patient: Breaking Past Diagnostic Boundaries.

Abstract

Background: Spinocerebellar ataxia type 3 (SCA3) is a neuromuscular disorder (NMD) that is a complicated and progressive genetic disorder. SCA3 is predominantly caused by repeat expansions (REs) of short tandem repeats (STRs). SCA3 is caused by a CAG repeat expansion of the ATXN3 gene and is transmitted in an autosomal dominant manner and located on chromosomal position 14q32.

Objective: The objective of this study was to identify the ATNX3 gene and assess the clinical accuracy of whole genome sequencing (WGS) in finding REs in previously undiagnosed patients with SCA3 for better management.

Methods and materials: Thirty-three referral cases for SCA3 were analyzed using WGS and triplet-repeat PCR (TP-PCR) techniques to detect REs for the ATXN3 gene.

Results: A case of SCA3 was discovered to be positive for the ATXN3 gene for 59 CAG REs revealed by WGS and validated by TP-PCR. This mutation was found in a 26-year-old male patient who had previously been undiagnosed by other genetic tests.

Conclusion: To identify REs in the ATXN3 gene by validating WGS with previously inconclusive genetic tests, the study propose that WGS could potentially be implemented as the frontline, cost-effective, less turnaround time molecular testing for more accurate diagnoses and better-informed treatment strategies.