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Identification and in silico analysis of GALNS mutations causing Morquio A syndrome in eight consanguineous families

Genetic deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) due to mutations in the GALNS gene results in the pathogenesis of Morquio A syndrome. To date, more than 200 mutations have been reported in GALNS, resulting in variable clinical features. | Turkish Journal of Biology Turk J Biol (2017) 41: 458-468 © TÜBİTAK doi:10.3906/biy-1607-81 http://journals.tubitak.gov.tr/biology/ Research Article Identification and in silico analysis of GALNS mutations causing Morquio A syndrome in eight consanguineous families 1 1 1 1 1 1 Irfan ULLAH , Abdul NASIR , Sarmad MEHMOOD , Sohail AHMED , Muhammad Ikram ULLAH , Asmat ULLAH , 2 1 1 3 4 1, Abdul AZIZ , Syed Irfan RAZA , Khadim SHAH , Saadullah KHAN , Muhammad Jawad HASSAN , Wasim AHMAD * 1 Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan 2 Department of Computer Science & Bioinformatics, Khushal Khan Khattak University, Karak, KPK, Pakistan 3 Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat, KPK, Pakistan 4 Atta ur Rahman School of Applied Biosciences, National University of Science & Technology (NUST), Islamabad, Pakistan Received: 31.07.2016 Accepted/Published Online: 08.01.2017 Final Version: 14.06.2017 Abstract: Genetic deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) due to mutations in the GALNS gene results in the pathogenesis of Morquio A syndrome. To date, more than 200 mutations have been reported in GALNS, resulting in variable clinical features. For this reason, bioinformatics analysis of these mutations is important to determine their effect on the structure and functions of the protein and to establish a correlation between genotype and phenotype. In the present study, eight Pakistani consanguineous families with Morquio A syndrome were clinically and genetically evaluated. Linkage analysis followed by sequence analysis of the gene detected four novel (p.Phe216Ser, p.Met38Arg, p.Ala291Ser, p.Glu121Argfs*37) and two reported (p.Pro420Arg, p.Arg386Cys) mutations in the eight families. In silico structural and functional analysis predicted that these mutations disrupt the function of GALNS protein through fluctuating its