title: Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex.
abstract: Mutations in PLA2G6 were identified in patients with a spectrum of neurodegenerative conditions, such as infantile neuroaxonal dystrophy (INAD), atypical late-onset neuroaxonal dystrophy (ANAD) and dystonia parkinsonism complex (DPC). However, there is no report on the genetic analysis of families with members affected with INAD, ANAD and DPC from India. Therefore, the main aim of this study was to perform genetic analysis of 22 Indian families with INAD, ANAD and DPC. DNA sequence analysis of the entire coding region of PLA2G6 identified 13 different mutations, including five novel ones (p.Leu224Pro, p.Asp283Asn, p.Arg329Cys, p.Leu491Phe, and p.Arg649His), in 12/22 (54.55%) families with INAD and ANAD. Interestingly, one patient with INAD was homozygous for two different mutations, p.Leu491Phe and p.Ala516Val, and thus harboured four mutant alleles. With these mutations, the total number of mutations in this gene reaches 129. The absence of mutations in 10/22 (45.45%) families suggests that the mutations could be in deep intronic or promoter regions of this gene or these families could have mutations in a yet to be identified gene. The present study increases the mutation landscape of PLA2G6. The present finding will be useful for genetic diagnosis, carrier detection and genetic counselling to families included in this study and other families with similar disease condition.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Saketh
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Mohd Hussain
authors.initials: MH
authors.lastname: Shah
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Mohammad Iqbal
authors.initials: MI
authors.lastname: Rather
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Bhat
authors.affiliation: Department of Biotechnology, R.V. College of Engineering, Bangalore, 560059, India.
authors.forename: Sindhura
authors.initials: S
authors.lastname: Gopinath
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Parayil Sankaran
authors.initials: PS
authors.lastname: Bindu
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Arun B
authors.initials: AB
authors.lastname: Taly
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Nagappa
authors.affiliation: Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Rose Dawn
authors.initials: RD
authors.lastname: Bharath
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahadevan
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Narayanappa
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
authors.forename: Yasha T
authors.initials: YT
authors.lastname: Chickabasaviah
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D004421:Dystonia / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics; D005091:Exons; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D019189:Iron Metabolism Disorders / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics*
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human