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

Authors : İrfan ULLAH, Abdul NASIR, Sarmad MEHMOOD, Sohail AHMED, Muhammad İkram ULLAH, Asmat ULLAH, Abdul AZIZ, Syed İrfan RAZA, Khadim SHAH, Saad Ullah KHAN, Muhammad Jawad HASSAN, Wasim AHMAD

Pages : 458-468

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Publication Date : 2017-12-01

Article Type : Research Paper

Abstract :Genetic deficiency of N-acetylgalactosamine-6-sulfate sulfatase insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(p.Phe216Ser, p.Met38Arg, p.Ala291Ser, p.Glu121Argfs*37); and two reported insert ignore into journalissuearticles values(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 three-dimensional structure, stability, and binding affinity and produce severe phenotypes. This is the first comprehensive study on molecular analysis of patients with Morquio A syndrome from Pakistan that reports four novel mutations with their structural and functional consequences.
Keywords : Morquio A syndrome, GALNS, missense mutations, in silico analysis