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Published on: November 21, 2013
Investigations of Huntington's Disease and Huntington's Disease-Like Syndromes in Indian Choreatic Patients
Jaslovleen Kaur1, Shaista Parveen2, Uzma Shamim2
1Department of Neurology, Dayanand Medical College & Hospital, Civil Lines, Ludhiana, India.
Insights
Genetic testing identified expanded HTT-CAG repeats in 59% of patients with choreiform disorders. SCA12 and SCA17 were identified as potential mimics of Huntington
Area of Science:
- Neurogenetics
- Movement Disorders
- Genetic Diagnosis
Background:
- Choreiform movement disorders, including Huntington's disease (HD), present complex diagnostic challenges.
- Differentiating HD from HD-like phenotypes requires sophisticated genetic analysis.
Purpose of the Study:
- To genetically characterize Huntington's disease (HD) and HD-like presentations in an Indian population.
- To investigate HTT-CAG expansion in families with neuroferritinopathy-like disorders.
Main Methods:
- 159 patients with suspected HD or HD-like disorders underwent genetic testing.
- Initial testing focused on HTT-CAG repeats, followed by screening for JPH3, TBP, ATN1, PPP2R2B (SCA12), and C9orf72 in HD-negative cases.
- Four families with neuroferritinopathy-like presentations were specifically tested for HTT-CAG expansion.
Main Results:
- Expanded HTT-CAG repeats were found in 59% (94/159) of patients.
- No pathogenic expansions were detected in JPH3, ATN1, or C9orf72.
- SCA12 expansions were identified in two patients, and SCA17 (TBP-CAG) expansions in five patients (reduced penetrance).
- Four families with neuroferritinopathy-like disorders showed HTT-CAG expansion.
Conclusions:
- SCA12 is identified as a novel phenocopy of HD, warranting inclusion in diagnostic workups for HD-like syndromes.
- SCA17 should also be considered in the differential diagnosis of HD-like presentations.
- The study highlights the importance of considering evolving HD-like phenotypes, including those mimicking neuroferritinopathy, for accurate clinical diagnosis.
Background:
The diagnostic workup for choreiform movement disorders including Huntington's disease (HD) and those mimicking HD like phenotype is complex.
Objective:
The aim of the present study was to genetically define HD and HD-like presentations in an Indian cohort. We also describe HTT-CAG expansion manifesting as neuroferritinopathy-like disorder in four families from Punjab in India.
Materials And Methods:
159 patients clinically diagnosed as HD and HD-like presentations from various tertiary neurology clinics were referred to our centre (CSIR-IGIB) for genetic investigations. As a first tier test, CAG-TNR for HTT was performed and subsequently HD-negative samples were screened for JPH3 (HDL2), TBP (SCA17), ATN1 (DRPLA), PPP2R2B (SCA12) and GGGGCC expansion in C9orf72 gene. Four families presenting as neuroferritinopathy-like disorder were also investigated for HTT-CAG expansion.
Results:
94 of 159 (59%) patients were found to have expanded HTT-CAG repeats. Pathogenic repeat expansion in JPH3, TBP, ATN1 and C9orf72 were not found in HD negative cases. Two patients were positive for SCA12-CAG expansion in pathogenic length, whereas 5 cases harboured TBP-CAG repeats falling in reduced penetrance range of 41- 48 repeats for SCA17. Four unrelated families, presented with atypical chorea and brain MRI findings suggestive of basal ganglia abnormalities mimicking neuroferritinopathy were found to harbour HTT-CAG expansion.
Conclusion:
We present SCA12 as a new reported phenocopy of HD which should be considered for diagnostic workout along with SCA17 for HD-like syndromes. This study also illustrates the necessity, to consider evolving HD like phenotype, as a clinical diagnosis for cases with initial manifestations depicting neuroferritinopathy.
