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A novel in-frame mutation in CLN3 leads to Juvenile neuronal ceroid lipofuscinosis in a large Pakistani family.
Sher, Muhammad; Farooq, Muhammad; Abdullah, Uzma; Ali, Zafar; Faryal, Sanam; Zakaria, Mohammad; Ullah, Farid; Bukhari, Hassan; Møller, Rikke S; Tommerup, Niels; Baig, Shahid Mahmood.
Afiliación
  • Sher M; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Farooq M; b Department of Bioinformatics and Biotechnology , Government College University Faisalabad , Pakistan.
  • Abdullah U; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Ali Z; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Faryal S; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Zakaria M; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Ullah F; c Department of Genetics , Hazara University , Mansehra , Pakistan.
  • Bukhari H; a Human Molecular Genetics Laboratory , National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS , Faisalabad , Pakistan.
  • Møller RS; d Radiology Department , Allied Hospital , Faisalabad , Pakistan.
  • Tommerup N; e Danish Epilepsy Centre, Institute for Regional Health Services , University of Southern Denmark , Odense , Denmark.
  • Baig SM; f Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research , University of Copenhagen , Copenhagen , Denmark.
Int J Neurosci ; 129(9): 890-895, 2019 Sep.
Article en En | MEDLINE | ID: mdl-30892110
Aim: Neuronal ceroid lipofuscinosis (NCLs) are the most common neurodegenerative disorders, with global incidence of 1 in 100,000 live births. NCLs affect central nervous system, primarily cerebellar and cerebral cortices. Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is the most common form of NCLs. JNCL is primarily caused by pathogenic mutations in CLN3 gene, which encodes a transporter transmembrane protein of uncertain function. The 1.02 kb deletion is the most common mutation in CLN3 that results in frame shift and a premature termination leading to nonfunctional protein. Here, we invetigated a large consanguineous family consisting of four affected individuals with clincal symptoms suggestive of Juvenile neuronal ceroid lipofuscinosis. Materials and methods: We conducted clinial and radilogical investigation of the family and performed NGS based Gene Panel sequencing comprising of five hundred and forty five candidate genes to characterize it at genetic level. Results: We identified a novel homozygous c.181_183delGAC mutation in the CLN3 gene seggregating witht the disorder in the family. The mutation induces in-frame deletion, deleting one amino acid (p.Asp61del) in CLN3 protein. The deleted amino acid aspartic acid plays an important role as general acid in enzymes active centers as well as in maintaining the ionic character of proteins. Conclusion: Our finding adds to genetic variability of Juvenile neuronal ceroid lipofuscinosis associated with CLN3 gene and a predicted CLN3 protein interacting domain site.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Chaperonas Moleculares / Mutación / Lipofuscinosis Ceroideas Neuronales Tipo de estudio: Prognostic_studies Límite: Adolescent / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Int J Neurosci Año: 2019 Tipo del documento: Article País de afiliación: Pakistán

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Chaperonas Moleculares / Mutación / Lipofuscinosis Ceroideas Neuronales Tipo de estudio: Prognostic_studies Límite: Adolescent / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Int J Neurosci Año: 2019 Tipo del documento: Article País de afiliación: Pakistán