How to Diagnose and Stage Huntington's Disease: A Brief Overview
Keywords:
Huntington’s Disease, Huntingtin (HTT), CAG trinucleotide repeat expansionAbstract
Huntington’s disease (HD) is a rare neurodegenerative disorder that entails progressive motor, cognitive and psychiatric dysfunctions due to a single gene mutation of CAG trinucleotide repeat expansion in the chromosome 4p16.3 in the Huntingtin (HTT) gene. An accurate diagnosis of HD is especially important due to the fact that this incurable disease inevitably leads to death. As HD is an autosomal dominant trait, a child of an affected parent has a 50% chance of inheriting the disease. Herein, a brief overview of diagnosing and staging HD is covered, including but not limited to Unified HD Rating Scale (UHDRS) for clinical testing, and modified polymerase chain reaction (PCR) and next-generation sequencing (NGS) methods for diagnostic genetic testing. Ultimately, it is the genetic testing of the CAG repeat length that confirms diagnosis. Emotional and social implications throughout the diagnostic process are discussed. In addition, the roles of various types of biomarkers including mutant huntingtin (mHTT) and neurofilament light chain (NfL) for predicting the onset of the disease, staging, monitoring the progression of HD, and management of interventions are discussed. Promising areas for future research are further mentioned.
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