| Popis: |
Masoumeh Dehghan Manshadi,1 Behnam Kamalidehghan,2,3 Omid Aryani,1 Elham Khalili,1 Sepideh Dadgar,1 Mahdi Tondar,4 Fatemeh Ahmadipour,5 Goh Yong Meng,6 Massoud Houshmand1,31Department of Medical Genetics, Special Medical Center, Tehran, Iran; 2Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Department of Biochemistry and Molecular & Cellular Biology, School of Medicine, Georgetown University, Washington, DC, USA; 5Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software. Here, 4 new pathogenic homozygous mutations c.585G>T, c.661T>A, c.849C>G, and c.911A>G were detected. The consequence of this study has extended the genotypic spectrum of MLD patients, paving way to a more effective method for carrier detection and genetic counseling. Keywords: psychomotor regression, demyelinating, gait abnormality and impairment, metachromatic leukodystrophy (MLD), behavioral disturbances |
