Document Type : Original Article
Authors
1 Researcher and lecture assistant at the Medical Laboratory Science Department, Knowledge University, Kurdistan Region, Erbil, Iraq
2 Department of Medical genetic, national Institute for genetic Engineering and Biotechnology, Tehran, Iran
3 Personalized Medicine Research Center of AmitisGen, Tehran, Iran
Abstract
Metachromatic leukodystrophyis a kind of lysosomal storage disorder caused by a deficiency in the ARSA enzyme, which is involved in the metabolism of membrane sulfatides into galactosylceramide. ARSA gene mutation analysis is likely to be in increasing demand for the accurate detection of heterozygous carriers and for prenatal diagnosis in families with a metachromatic leukodystrophy proband. This study examined the sequence of the ARSA gene in 7 patients with metachromatic leukodystrophy by exon Sanger sequencing. Eleven mutations were found in the ARSA gene. It was further found that five mutations were probably damaging to the protein activity with a high score and specificity. The results pave the way to a more effective method for career detection , genetic diagnosis, and the counseling of Iranian patients with MLD disorder.
Keywords
- an Egmond ME, Pouwels PJ, Boelens JJ, et al. Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy. JAMA Neurol. 2013;70(6):779–782.
- Wang RY, Bodamer OA, Watson MS, Wilcox WR; ACMG Work Group on Diagnostic Confirmation of Lysosomal Storage Diseases. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet Med. 2011;13(5):457–484.
- Cheon JE, Kim IO, Hwang YS, et al. Leukodystrophy in children: a pictorial review of MR imaging features. Radiographics. 2002;.
- Eichler F, Grodd W, Grant E, et al. Metachromatic leukodystrophy: a scoring system for brain MR imaging observations. AJNR Am J 2009;30(10):1893–1897.
- Molzer B, Sundt-Heller R, Kainz-Korschinsky M, Zobel M. Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy: dependence on reduction of arylsulfatase A activity. Am J Med Genet.
- Gort L, Coll MJ, Chabás A. Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients. Hum Mutat. 1999;14(3):240–248.
- Kreysing J, von Figura K, Gieselmann V. Structure of the arylsulfatase A gene. Eur J Biochem. 1990;191(3):627–631.
- Polten A, Fluharty AL, Fluharty CB, Kappler J, von Figura K, Gieselmann V. Molecular basis of different forms of metachromatic leukodystrophy. N Engl J Med. 1991;324(1):18–22
- Berger J, Löschl B, Bernheimer H, et al. Occurrence, distribution, and phenotype of arylsulfatase A mutations in patients with metachromatic leukodystrophy. Am J Med Genet. 1997;69(3):335–340.
- Schestag F, Yaghootfam A, Habetha M, et al. The functional consequences Of mis-sense mutations affecting an intra-molecular salt bridge In arylsulphatase A. Biochem J.2002;367(Pt 2):499–504.
- Gieselmann V, Franken S, Klein D, et al. Metachromatic leukodystrophy: consequences of sulphatide accumulation. Acta Paediatr Suppl. 2003;92(443):74–79; discussion 45.
)