Advertisement

Identification of eleven different mutations including six novel, in the arylsulfatase B gene in Iranian patients with mucopolysaccharidosis type VI

  • Rokhsareh Jafaryazdi
  • Sedigheh Shams
  • Anna Isaian
  • Aria Setoodeh
  • Shahram TeimourianEmail author
Original Article

Abstract

Mucopolysaccharidosis VI is a rare autosomal recessive disorder caused by the deficiency of enzyme Arylsulfatase B. The enzyme deficiency leads to the accumulation of dermatan sulfate in connective tissue which causes manifestations related to MPS VI. Up to now, three different disease causing variants are reported in Iranian patients. In this study, we scanned ARSB gene of 13 Iranian patients from 12 families in whom all parents were consanguineous and from the same ethnicity except one family that were not consanguineous but co-ethnic. We found six not previously reported disease causing variants. We extracted DNA from peripheral blood samples of patients that were previously confirmed as MPS VI by clinical, biochemical and enzymatic assays including berry-spot test and fluorimetry, followed by PCR and direct sequencing. Computational approaches were used to analyze novel variants in terms of their impact on the protein structure. 11 disease causing variants and 15 polymorphisms were found. Six disease causing variants were novel and five were previously reported of which three were in Iranian population. Four of patients, who were unrelated, two by two had the same disease causing variant and polymorphisms, which indicates a possible founder effect. Our study also implicates genotype–phenotype correlation. Computational structural modeling indicated these disease causing variants might affect structural stability and function of the protein. Data of this study confirms the existence of mutational heterogeneity in the ARSB between Iranian patients. Disease causing variants with high frequency can be used in the prenatal diagnosis and genetic counseling. Also, the existence of the same variants and polymorphisms in some of the unrelated patients indicates a possible founder effect.

Keywords

Arylsulfatase B MPS VI In silico Iran Sanger sequencing Variant 

Notes

Acknowledgments

The authors appreciate the patient family who kindly contributed to this study. The authors thank Ms. Neda Konkouri and Ms. Zhilla Poursheikhi who helped us in the blood sampling process. The authors declare there is no conflict of interest.

Funding

This study is funded by Iran University of medical sciences (IUMS), Iran. Grant Number 96-03-30-30735. This study is part of Miss. Jafaryazdi MSc thesis.

Compliance with ethical standards

Conflict of interest

The authors declare there is no conflict of interests.

Ethical approval

All of the ethical standards were approved by the responsible committee (Iran University of Medical Sciences, Faculty of Medicine).

Informed consent

All participants or their parents, whenever needed, signed informed consent forms.

Supplementary material

11033_2019_4804_MOESM1_ESM.docx (270 kb)
Supplementary material 1 (DOCX 269 kb)
11033_2019_4804_MOESM2_ESM.docx (1 mb)
Supplementary material 2 (DOCX 1068 kb)

References

  1. 1.
    Muenzer J (2011) Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 50(Suppl 5):v4–v12.  https://doi.org/10.1093/rheumatology/ker394 CrossRefGoogle Scholar
  2. 2.
    Hendriksz CJ et al (2011) Design, baseline characteristics, and early findings of the MPS VI (mucopolysaccharidosis VI) Clinical Surveillance Program (CSP). J Inherit Metab Dis 36(2):373–384.  https://doi.org/10.1007/s10545-011-9410-9 CrossRefGoogle Scholar
  3. 3.
    Vougioukas I, Berlis A, Kopp MV, Korinthenberg R, Spreer J, van Velthoven V (2001) Neurosurgical interventions in children with Maroteaux-Lamy syndrome. Case report and review of the literature. Pediatr Neurosurg 35(1):35–38CrossRefGoogle Scholar
  4. 4.
    Miller G, Partridge A (1983) Mucopolysaccharidosis type VI presenting in infancy with endocardial fibroelastosis and heart failure. Pediatr Cardiol 4(1):61–62CrossRefGoogle Scholar
  5. 5.
    Smith KS, Hallett KB, Hall RK, Wardrop RW, Firth N (1995) Mucopolysaccharidosis: MPS VI and associated delayed tooth eruption. Int J Oral Maxillofac Surg 24(2):176–180CrossRefGoogle Scholar
  6. 6.
    Valayannopoulos V, Nicely H, Harmatz P, Turbeville S (2010) Mucopolysaccharidosis VI. Orphanet J Rare Dis 5:5.  https://doi.org/10.1186/1750-1172-5-5 CrossRefGoogle Scholar
  7. 7.
    Fong LV, Menahem S, Wraith JE, Chow CW (1987) Endocardial fibroelastosis in mucopolysaccharidosis type VI. Clin Cardiol 10(6):362–364CrossRefGoogle Scholar
  8. 8.
    Hayflick S, Rowe S, Kavanaugh-McHugh A, Olson JL, Valle D (1992) Acute infantile cardiomyopathy as a presenting feature of mucopolysaccharidosis VI. J Pediatr 120(2 Pt 1):269–272CrossRefGoogle Scholar
  9. 9.
    Swiedler SJ et al (2005) Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Am J Med Genet A 134a(2):144–150.  https://doi.org/10.1002/ajmg.a.30579 CrossRefGoogle Scholar
  10. 10.
    Choy YS et al (2015) Identifying the need for a multidisciplinary approach for early recognition of mucopolysaccharidosis VI (MPS VI). Mol Genet Metab 115(1):41–47.  https://doi.org/10.1016/j.ymgme.2015.03.005 CrossRefGoogle Scholar
  11. 11.
    Brooks DA, Gibson GJ, Karageorgos L, Hein LK, Robertson EF, Hopwood JJ (2005) An index case for the attenuated end of the mucopolysaccharidosis type VI clinical spectrum. Mol Genet Metab 85(3):236–238.  https://doi.org/10.1016/j.ymgme.2005.02.008 CrossRefGoogle Scholar
  12. 12.
    Harmatz P, Shediac R (2017) Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment. Front Biosci (Landmark Ed) 22:385–406CrossRefGoogle Scholar
  13. 13.
    Litjens T, Baker EG, Beckmann KR, Morris CP, Hopwood JJ, Callen DF (1989) Chromosomal localization of ARSB, the gene for human N-acetylgalactosamine-4-sulphatase. Hum Genet 82(1):67–68CrossRefGoogle Scholar
  14. 14.
    Jurecka A et al (2012) Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia. Mol Genet Metab 105(2):237–243.  https://doi.org/10.1016/j.ymgme.2011.11.003 CrossRefGoogle Scholar
  15. 15.
    S. Abbasi, M. Noruzinia, O. Bashti, M. Ahmadvand, A. R. S. Chaleshtori, and L. Mahootipou (2017), Another Novel Missense Mutation in ARSB Gene in Iran. Acta Med Iran, Case Report(s) vol. 55, no. 9, pp. 585-590. http://acta.tums.ac.ir/index.php/acta/article/view/5759
  16. 16.
    Nouri N, Nouri N, Aryani O, Kamalidehghan B, Houshmand M (2012) Identification of a novel arylsulfatase B gene mutation in three unrelated Iranian mucopolysaccharidosis type-VI patients with different phenotype severity. Iran Biomed J 16(3):169–171Google Scholar
  17. 17.
    Mabe P, Valiente A, Soto V, Cornejo V, Raimann E (2004) Evaluation of reliability for urine mucopolysaccharidosis screening by dimethylmethylene blue and Berry spot tests. Clin Chim Acta 345(1–2):135–140.  https://doi.org/10.1016/j.cccn.2004.03.015 CrossRefGoogle Scholar
  18. 18.
    Jafaryazdi R, Shams S, Isaian A, Ebadi E, Teimourian SH (2018) A novel compound heterozygote mutation in the ARSB gene in a patient with Maroteaux-Lamy syndrome and its Insilico evaluatio—ScienceDirect. Metagene 18:127–131.  https://doi.org/10.1016/j.mgene.2018.08.013 Google Scholar
  19. 19.
    Fujikura K (2015) No-wash ethanol precipitation of dye-labeled reaction products improves DNA sequencing reads. Anal Biochem 468:39–41.  https://doi.org/10.1016/j.ab.2014.09.010 CrossRefGoogle Scholar
  20. 20.
    Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11(4):361–362CrossRefGoogle Scholar
  21. 21.
    Tang H, Thomas PD (2016) PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation. Bioinformatics 32(14):2230–2232.  https://doi.org/10.1093/bioinformatics/btw222 CrossRefGoogle Scholar
  22. 22.
    Richards S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424.  https://doi.org/10.1038/gim.2015.30 CrossRefGoogle Scholar
  23. 23.
    Bond CS et al (1997) Structure of a human lysosomal sulfatase. Structure 5(2):277–289.  https://doi.org/10.1016/s0969-2126(97)00185-8 CrossRefGoogle Scholar
  24. 24.
    Lovell SC et al (2002) Structure validation by Calpha geometry: phi, psi and Cbeta deviation. Proteins: Struct, Funct Genet 50:437–450CrossRefGoogle Scholar
  25. 25.
    Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G (2010) Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinform 11:548.  https://doi.org/10.1186/1471-2105-11-548 CrossRefGoogle Scholar
  26. 26.
    Karageorgos L et al (2007) Mutational analysis of 105 mucopolysaccharidosis type VI patients. Hum Mutat 28(9):897–903.  https://doi.org/10.1002/humu.20534 CrossRefGoogle Scholar
  27. 27.
    Litjens T, Morris CP, Robertson EF, Peters C, von Figura K, Hopwood JJ (1992) An N-acetylgalactosamine-4-sulfatase mutation (delta G238) results in a severe Maroteaux-Lamy phenotype. Hum Mutat 1(5):397–402.  https://doi.org/10.1002/humu.1380010509 CrossRefGoogle Scholar
  28. 28.
    Villani GR, Balzano N, Vitale D, Saviano M, Pavone V, Di Natale P (1999) Maroteaux-lamy syndrome: five novel mutations and their structural localization. Biochim Biophys Acta 1453(2):185–192CrossRefGoogle Scholar
  29. 29.
    Garrido E et al (2007) Identification of the molecular defects in Spanish and Argentinian mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) patients, including 9 novel mutations. Mol Genet Metab 92(1–2):122–130.  https://doi.org/10.1016/j.ymgme.2007.06.002 CrossRefGoogle Scholar
  30. 30.
    Chistiakov DA et al (2014) Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia. Clin Chim Acta 436:112–120.  https://doi.org/10.1016/j.cca.2014.05.010 CrossRefGoogle Scholar
  31. 31.
    Petry MF et al (2005) Mucopolysaccharidosis type VI: identification of novel mutations on the arylsulphatase B gene in South American patients. J Inherit Metab Dis 28(6):1027–1034.  https://doi.org/10.1007/s10545-005-0020-2 CrossRefGoogle Scholar
  32. 32.
    Isbrandt D, Arlt G, Brooks DA, Hopwood JJ, von Figura K, Peters C (1994) Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes. Am J Hum Genet 54(3):454–463Google Scholar
  33. 33.
    Zanetti A et al (2014) Molecular analysis of Turkish Maroteaux-Lamy patients and identification of one novel mutation in the arylsulfatase B (ARSB) gene. JIMD Rep 14:1–9.  https://doi.org/10.1007/8904_2013_276 Google Scholar
  34. 34.
    Karageorgos L et al (2007) Mutational analysis of mucopolysaccharidosis type VI patients undergoing a phase II trial of enzyme replacement therapy. Mol Genet Metab 90(2):164–170.  https://doi.org/10.1016/j.ymgme.2006.10.008 CrossRefGoogle Scholar
  35. 35.
    Lin WD et al (2008) Genetic analysis of mucopolysaccharidosis type VI in Taiwanese patients. Clin Chim Acta 394(1–2):89–93.  https://doi.org/10.1016/j.cca.2008.04.014 Google Scholar
  36. 36.
    Voskoboeva E, Krasnopol’skaia KD, Peters K, von Figura K (2000) Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients. Genetika 36(6):837–843Google Scholar
  37. 37.
    Yang CF, Wu JY, Lin SP, Tsai FJ (2001) Mucopolysaccharidosis type VI: report of two Taiwanese patients and identification of one novel mutation. J Formos Med Assoc 100(12):820–823Google Scholar
  38. 38.
    Karageorgos L et al (2004) Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy. Hum Mutat 23(3):229–233.  https://doi.org/10.1002/humu.10313 CrossRefGoogle Scholar
  39. 39.
    Ley-Martos M et al (2018) Family study of a novel mutation of mucopolysaccharidosis type VI with a severe phenotype and good response to enzymatic replacement therapy: case report. Medicine (Baltimore) 97(42):e12872.  https://doi.org/10.1097/md.0000000000012872 CrossRefGoogle Scholar
  40. 40.
    Malekpour N, Vakili R, Hamzehloie T (2018) Mutational analysis of ARSB gene in mucopolysaccharidosis type VI identification of three novel mutations in Iranian patients. Iran J Basic Med Sci 21(9):950–956.  https://doi.org/10.22038/ijbms.2018.27742.6760 Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Rokhsareh Jafaryazdi
    • 1
  • Sedigheh Shams
    • 2
    • 3
    • 4
  • Anna Isaian
    • 2
    • 3
  • Aria Setoodeh
    • 5
  • Shahram Teimourian
    • 1
    Email author
  1. 1.Department of Medical Genetics and Molecular BiologyIran University of Medical SciencesTehranIran
  2. 2.Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical SciencesTehranIran
  3. 3.Department of PathologyTehran University of Medical SciencesTehranIran
  4. 4.Pediatric Urology Research Center, Tehran University of Medical SciencesTehranIran
  5. 5.Division of Pediatrics Endocrinology, Children’s Medical CenterPediatrics Center of Excellence, Tehran University of Medical SciencesTehranIran

Personalised recommendations