Pratiksha Chheda1, Milind Chanekar2, Yogita Salunkhe2, Tavisha Dama2, Anurita Pais3, Shailesh Pande3, Rajesh Bendre2, Nilesh Shah2. 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. pratiksha.chheda@metropolisindia.com. 2. 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. 3. Genetics Department, Metropolis Healthcare Ltd, Mumbai, 400 070, India.
Abstract
BACKGROUND: Huntington's disease (HD) is an autosomal-dominant 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 most accurate and comprehensive molecular diagnostic evaluation of HD.
BACKGROUND:Huntington's disease (HD) is an autosomal-dominant 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 most accurate and comprehensive molecular diagnostic evaluation of HD.
Authors: S Raskin; N Allan; H A Teive; F Cardoso; M S Haddad; G Levi; R Boy; J Lerena Junior; V S Sotomaior; M Janzen-Dück; L B Jardim; F R Fellander; L A Andrade Journal: Arq Neuropsiquiatr Date: 2000-12 Impact factor: 1.420
Authors: Nancy S Wexler; Judith Lorimer; Julie Porter; Fidela Gomez; Carol Moskowitz; Edith Shackell; Karen Marder; Graciela Penchaszadeh; Simone A Roberts; Javier Gayán; Denise Brocklebank; Stacey S Cherny; Lon R Cardon; Jacqueline Gray; Stephen R Dlouhy; Sandra Wiktorski; Marion E Hodes; P Michael Conneally; Jack B Penney; James Gusella; Jang-Ho Cha; Michael Irizarry; Diana Rosas; Steven Hersch; Zane Hollingsworth; Marcy MacDonald; Anne B Young; J Michael Andresen; David E Housman; Margot Mieja De Young; Ernesto Bonilla; Theresa Stillings; Americo Negrette; S Robert Snodgrass; Maria Dolores Martinez-Jaurrieta; Maria A Ramos-Arroyo; Jacqueline Bickham; Juan Sanchez Ramos; Frederick Marshall; Ira Shoulson; Gustavo J Rey; Andrew Feigin; Norman Arnheim; Amarilis Acevedo-Cruz; Leticia Acosta; Jose Alvir; Kenneth Fischbeck; Leslie M Thompson; Angela Young; Leon Dure; Christopher J O'Brien; Jane Paulsen; Adam Brickman; Denise Krch; Shelley Peery; Penelope Hogarth; Donald S Higgins; Bernhard Landwehrmeyer Journal: Proc Natl Acad Sci U S A Date: 2004-03-01 Impact factor: 11.205