Biopolym. Cell. 2016; 32(6):442-449.
Molecular Biomedicine
Molecular-genetic characterization of Ukrainian patients with mucopolysaccharidosis I: identification of three new mutations in α-L-iduronidase gene
1, 2Trofimova N. S., 1, 2Olkhovich N. V.
- National Children's Specialized Hospital Okhmatdyt, Ministry of Health of Ukraine
28/1, Chornovola Str., Kyiv, Ukraine, 01135 - State Institute of Genetic and Regenerative Medicine, NAMS of Ukraine
67, Vyshhorodska Str., Kyiv, Ukraine, 04114
Abstract
Mucopolysaccharidosis I (MPS I) is a rare hereditary autosomal-recessive metabolic disorder, which occurs due to the deficiency of the lysosomal enzyme α-L-iduronidase (IDUA; EC 3.2.1.76). There are three clinical forms of MPS I: Hurler syndrome, MPS I H; MIM # 607014, ORPHA 93473, Hurler/Scheie syndrome, MPS I H/S; MIM # 607015, ORPHA 93476, Scheie syndrome, MPS I S; MIM # 607016, ORPHA 93474. Aim. To identify the spectrum of mutations in the IDUA gene in Ukrainian patients with MPS I. Methods. RFLP-analysis, automated sequencing. Results. We have identified 100 % (34/34) mutant alleles of the IDUA gene among 18 Ukrainian patients (one proband had a sibling with the identical genotype) with MPS I from 17 families. The spectrum of mutations in the IDUA gene in Ukrainian patients with MPS I is represented by six known missence mutations: p.Q70*, p.W402*, p.A75T, p.A327P, p.P533L, p.S633I; two deletions: c.1398delC and c.46_57del_12, one insertion: c.889_899_ins_12, and one mutation in the splicing zone IVS11ds+5G–A. Three new missence mutations were revealed by us in the IDUA gene: p.N372S, p.Q563P and p.S633*. Conclusions. Our results may be used for planning the most reasonable algorithm of the molecular-genetic analysis of Ukrainian patients with MPS I.
Keywords: mucopolysaccharidosis, Hurler syndrome, Scheie syndrome, α-L-iduronidase
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References
[1]
Mehta A, Winchester B. Lysosomal storage disorders: a practical guide. London: Wiley-Blackwell, 2012;94-100.
[2]
Clarke LA (Updated [September 21, 2007]). Mucopolysaccharidosis Type I. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2007.
[3]
Scott HS, Guo XH, Hopwood JJ, Morris CP. Structure and sequence of the human alpha-L-iduronidase gene. Genomics. 1992;13(4):1311-3.
[4]
Bertola F, Filocamo M, Casati G, Mort M, Rosano C, Tylki-Szymanska A, Tüysüz B, Gabrielli O, Grossi S, Scarpa M, Parenti G, Antuzzi D, Dalmau J, Di Rocco M, Dionisi Vici C, Okur I, Rosell J, Rovelli A, Furlan F, Rigoldi M, Biondi A, Cooper DN, Parini R. IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. Hum Mutat. 2011;32(6):E2189-210.
[5]
Wang X, Zhang W, Shi H, Qiu Z, Meng Y, Yao F, Wei M. Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis. Clin Genet. 2012;81(5):443-52.
[6]
Chistiakov DA, Savost'anov KV, Kuzenkova LM, Gevorkyan AK, Pushkov AA, Nikitin AG, Pakhomov AV, Vashakmadze ND, Zhurkova NV, Podkletnova TV, Mayansky NA, Namazova-Baranova LS, Baranov AA. Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia. Clin Chim Acta. 2014;436:112-20.
[7]
Trofimova NS, Olkhovich NV, Gorovenko NG. Optimization of biochemical and molecular genetic diagnostics of I type mucopolysaccharidoses in Ukraine. Achievements of Biology and Medicine. 2014; 1(23):61–5.
[8]
Bunge S, Kleijer WJ, Steglich C, Beck M, Zuther C, Morris CP, Schwinger E, Hopwood JJ, Scott HS, Gal A. Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients. Hum Mol Genet. 1994;3(6):861-6.
[9]
Clarke LA, Scott HS. Two novel mutations causing mucopolysaccharidosis type I detected by single strand conformational analysis of the alpha-L-iduronidase gene. Hum Mol Genet. 1993;2(8):1311-2.
[10]
Clarke LA, Nelson PV, Warrington CL, Morris CP, Hopwood JJ, Scott HS. Mutation analysis of 19 North American mucopolysaccharidosis type I patients: identification of two additional frequent mutations. Hum Mutat. 1994;3(3):275-82.
[11]
Bunge S, Kleijer WJ, Steglich C, Beck M, Schwinger E, Gal A. Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene. Hum Mutat. 1995;6(1):91-4.
[12]
Scott HS, Litjens T, Hopwood JJ, Morris CP. A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype. Hum Mutat. 1992;1(2):103-8.
[13]
Voskoboeva EY, Krasnopolskaya XD, Mirenburg TV, Weber B, Hopwood JJ. Molecular genetics of mucopolysaccharidosis type I: mutation analysis among the patients of the former Soviet Union. Mol Genet Metab. 1998;65(2):174-80.
[14]
Venturi N, Rovelli A, Parini R, Menni F, Brambillasca F, Bertagnolio F, Uziel G, Gatti R, Filocamo M, Donati MA, Biondi A, Goldwurm S. Molecular analysis of 30 mucopolysaccharidosis type I patients: evaluation of the mutational spectrum in Italian population and identification of 13 novel mutations. Hum Mutat. 2002;20(3):231.
[15]
Beesley CE, Meaney CA, Greenland G, Adams V, Vellodi A, Young EP, Winchester BG. Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum Genet. 2001;109(5):503-11.
