A Study of Triplet-Primed PCR for Identification of CAG Repeat Expansion in the HTT Gene in a Cohort of 503 Indian Cases
- PDF / 869,349 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 79 Downloads / 185 Views
SHORT COMMUNICATION
A Study of Triplet-Primed PCR for Identification of CAG Repeat Expansion in the HTT Gene in a Cohort of 503 Indian Cases with Huntington’s Disease Symptoms Pratiksha Chheda1 • Milind Chanekar1 • Yogita Salunkhe1 • Tavisha Dama1 Anurita Pais2 • Shailesh Pande2 • Rajesh Bendre1 • Nilesh Shah1
•
Ó Springer International Publishing AG, part of Springer Nature 2018
Abstract Background Huntington’s disease (HD) is an autosomaldominant neurodegenerative disorder with an average age at onset of 40 years. It is a polyglutamine (polyQ) disorder that is caused by an increase in the number of CAG repeats in the huntingtin (HTT) gene. Genetic tests that accurately determine the number of CAG repeats are performed for confirmation of diagnosis, predictive testing of persons at genetic risk for inheriting HD, and prenatal testing. The aim of our study was to evaluate efficacy of triplet-primed polymerase chain reaction (TP-PCR) for routine diagnosis of HD in suspected cases from India. Methods We evaluated a combination of CAG flanking PCR and triplet-primed PCR for estimation of CAG repeats in 503 cases with clinical suspicion of HD. Results There were 250 cases (49.7%) that showed the presence of expanded alleles, with 241 (47.9%) being fully penetrant alleles and nine (1.8%) in the reduced penetrance category. There were seven juvenile cases with an age of onset of \ 20 years, with the longest allele comprising 106 CAG repeats found in an 8-year-old male patient. The results demonstrated an inverse (R = - 0.67) relationship between CAG length and age at clinical onset. Conclusion Our study on pan-Indian cases is one of the largest studies reported so far in India and focuses on the
& Pratiksha Chheda [email protected] 1
Department of Molecular Pathology, Metropolis Healthcare Ltd, Commercial Building A, Unit No. 409 to 416, 4th Floor, Kohinoor City, Near Kohinoor Mall, Kirol Road, Kurla-W, Mumbai 400 070, India
2
Genetics Department, Metropolis Healthcare Ltd, Mumbai 400 070, India
most accurate and comprehensive molecular diagnostic evaluation of HD.
Key Points CAG flanking polymerase chain reaction (PCR) and triplet-primed PCR (TP-PCR) differentiate normal, intermediate, premutated, and fully mutated alleles, thereby confirming clinical diagnosis of Huntington’s disease (HD) in premutated and fully mutated alleles. In line with previous studies there was an inverse relationship between CAG repeats and age at clinical onset. There were seven juvenile cases of HD, each with an expanded allele. This is the first study on a pan-Indian population (503 cases).
1 Background Huntington’s disease (HD) is a fatal rare, progressive, autosomal-dominant, neurodegenerative genetic disorder. The majority of cases show adult onset along with the clinical triad of movement abnormality, emotional disturbance, and cognitive impairment that currently provide the basis for the clinical diagnosis of HD [1]. A higher prevalence of HD is seen in people of European ancestry (2.5–10/ 100,000) in compa
Data Loading...
