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Endocrine

, Volume 66, Issue 2, pp 185–191 | Cite as

Clinical and molecular assessment of 13 Iranian families with Wolfram syndrome

  • Maryam Sobhani
  • Mohammad Amin Tabatabaiefar
  • Soudeh Ghafouri-Fard
  • Asadollah Rajab
  • Sarah Mozafarpour
  • Samaneh Nasrniya
  • Abdol-Mohammad Kajbafzadeh
  • Mohammad Reza Noori-DaloiiEmail author
Original Article

Abstract

Purpose

Wolfram syndrome (WS) is a rare genetic disorder described by a pattern of clinical manifestations such as diabetes mellitus, diabetes insipidus, optic nerve atrophy, sensorineural hearing loss, urinary tract abnormalities, and psychiatric disorders. WFS1 and WFS2 loci are the main genetic loci associated with this disorder.

Methods

In the current study, we investigated associations between these loci and WS via STR markers and homozygosity mapping in 13 Iranian families with WS. All families were linked to WFS1 locus.

Results

Mutation analysis revealed four novel mutations (Q215X, E89X, S168Del, and E391Sfs*51) in the assessed families. Bioinformatics tools confirmed the pathogenicity of the novel mutations. Other identified mutations were previously reported in other populations for their pathogenicity.

Conclusions

The current study adds to the mutation repository of WS and shows a panel of mutations in Iranian population. Such panel would facilitate genetic counseling and prenatal diagnosis in families with WS cases.

Keywords

Wolfram Syndrome WFS1 

Notes

Acknowledgements

The current study was supported by a grant from Tehran University of Medical Sciences.

Funding

This study was funded by a grant from Tehran University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    T. Hershey, H.M. Lugar, J.S. Shimony, J. Rutlin, J.M. Koller, D.C. Perantie, A.R. Paciorkowski, S.A. Eisenstein, M.A. Permutt, Washington University Wolfram Study, G.: early brain vulnerability in Wolfram syndrome. PloS ONE 7(7), e40604 (2012).  https://doi.org/10.1371/journal.pone.0040604 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    R.G. Swift, D.B. Sadler, M. Swift, Psychiatric findings in Wolfram syndrome homozygotes. Lancet 336(8716), 667–669 (1990)CrossRefGoogle Scholar
  3. 3.
    S. Mozafarpour, A.M. Kajbafzadeh, A. Mojtahed, M. Mojtahed, H. Mahboubi, K. Shalileh, Management of bladder dysfunction in Wolfram syndrome with Mitrofanoff appendicovesicostomy: long-term follow-up. J. Pediatr. Surg. (2014).  https://doi.org/10.1016/j.jpedsurg.2014.09.058 CrossRefGoogle Scholar
  4. 4.
    M. Sobhani, M.A. Tabatabaiefar, A. Rajab, A.M. Kajbafzadeh, M.R. Noori-Daloii, Significant expressivity of Wolfram syndrome: phenotypic assessment of two known and one novel mutation in the WFS1 gene in three Iranian families. Mol. Biol. Rep. 41(11), 7499–7505 (2014).  https://doi.org/10.1007/s11033-014-3642-3 CrossRefPubMedGoogle Scholar
  5. 5.
    H. Inoue, Y. Tanizawa, J. Wasson, P. Behn, K. Kalidas, E. Bernal-Mizrachi, M. Mueckler, H. Marshall, H. Donis-Keller, P. Crock, D. Rogers, M. Mikuni, H. Kumashiro, K. Higashi, G. Sobue, Y. Oka, M.A. Permutt, A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat. Genet. 20(2), 143–148 (1998).  https://doi.org/10.1038/2441 CrossRefPubMedGoogle Scholar
  6. 6.
    T.M. Strom, K. Hortnagel, S. Hofmann, F. Gekeler, C. Scharfe, W. Rabl, K.D. Gerbitz, T. Meitinger, Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum. Mol. Genet 7(13), 2021–2028 (1998).  https://doi.org/10.1093/hmg/7.13.2021 CrossRefPubMedGoogle Scholar
  7. 7.
    G. Boutzios, S. Livadas, E. Marinakis, N. Opie, F. Economou, E. Diamanti-Kandarakis, Endocrine and metabolic aspects of the Wolfram syndrome. Endocrine 40(1), 10–13 (2011).  https://doi.org/10.1007/s12020-011-9505-y CrossRefPubMedGoogle Scholar
  8. 8.
    J. Kawano, R. Fujinaga, K. Yamamoto-Hanada, Y. Oka, Y. Tanizawa, K. Shinoda, Wolfram syndrome 1 (Wfs1) mRNA expression in the normal mouse brain during postnatal development. Neurosci. Res. 64(2), 213–230 (2009).  https://doi.org/10.1016/j.neures.2009.03.005 CrossRefPubMedGoogle Scholar
  9. 9.
    J. Grenier, I. Meunier, V. Daien, C. Baudoin, F. Halloy, B. Bocquet, C. Blanchet, C. Delettre, E. Esmenjaud, A. Roubertie, G. Lenaers, C.P. Hamel, WFS1 in optic neuropathies: mutation findings in nonsyndromic optic atrophy and assessment of clinical severity. Ophthalmology 123(9), 1989–1998 (2016).  https://doi.org/10.1016/j.ophtha.2016.05.036 CrossRefPubMedGoogle Scholar
  10. 10.
    M. Sobhani, M.A. Tabatabaiefar, A. Rajab, A.M. Kajbafzadeh, M.R. Noori-Daloii, Molecular characterization of WFS1 in an Iranian family with Wolfram syndrome reveals a novel frameshift mutation associated with early symptoms. Gene 528(2), 309–313 (2013).  https://doi.org/10.1016/j.gene.2013.06.040 CrossRefPubMedGoogle Scholar
  11. 11.
    T.G. Barrett, M. Scott-Brown, A. Seller, A. Bednarz, K. Poulton, J. Poulton, The mitochondrial genome in Wolfram syndrome. J. Med. Genet. 37(6), 463–466 (2000)CrossRefGoogle Scholar
  12. 12.
    Y. Noguchi, T. Yashima, A. Hatanaka, M. Uzawa, M. Yasunami, A. Kimura, K. Kitamura, A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss. Acta Otoaryngol. 125(11), 1189–1194 (2005)CrossRefGoogle Scholar
  13. 13.
    K.A. Pickett, R.P. Duncan, A.R. Paciorkowski, M.A. Permutt, B. Marshall, T. Hershey, G.M. Earhart; Washington University Wolfram Study, G., Balance impairment in individuals with Wolfram syndrome. Gait posture 36(3), 619–624 (2012).  https://doi.org/10.1016/j.gaitpost.2012.06.008 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    T. Barrett, S. Bundey, A. Macleod, Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 346(8988), 1458–1463 (1995)CrossRefGoogle Scholar
  15. 15.
    M. Saadat, M. Ansari-Lari, D.D. Farhud, Consanguineous marriage in Iran. Ann. Hum. Biol. 31(2), 263–269 (2004).  https://doi.org/10.1080/03014460310001652211 CrossRefPubMedGoogle Scholar
  16. 16.
    S. Ari, U. Keklikci, I. Caca, K. Unlu, H. Kayabasi, Wolfram syndrome: case report and review of the literature. Compr. Ther. 33(1), 18–20 (2007)CrossRefGoogle Scholar
  17. 17.
    M. Al-Till, N.S. Jarrah, K.M. Ajlouni, Ophthalmologic findings in fifteen patients with Wolfram syndrome. Eur. J. Ophthalmol. 12(2), 84–88 (2002)CrossRefGoogle Scholar
  18. 18.
    A. Cano, L. Molines, R. Valero, G. Simonin, V. Paquis-Flucklinger, B. Vialettes; French Group of Wolfram, S., Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes. Diabetes Care 30(9), 2327–2330 (2007).  https://doi.org/10.2337/dc07-0380 CrossRefPubMedGoogle Scholar
  19. 19.
    J. Rohayem, C. Ehlers, B. Wiedemann, R. Holl, K. Oexle, O. Kordonouri, G. Salzano, T. Meissner, W. Burger, E. Schober, A. Huebner, M.A. Lee-Kirsch, Wolfram syndrome diabetes writing, G.: diabetes and neurodegeneration in Wolfram syndrome: a multicenter study of phenotype and genotype. Diabetes Care 34(7), 1503–1510 (2011).  https://doi.org/10.2337/dc10-1937 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    A. Colosimo, V. Guida, L. Rigoli, C. Di Bella, A. De Luca, S. Briuglia, L. Stuppia, D.C. Salpietro, B. Dallapiccola, Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. Hum. Mutat. 21(6), 622–629 (2003).  https://doi.org/10.1002/humu.10215 CrossRefPubMedGoogle Scholar
  21. 21.
    J.M. van ven Ouweland, K. Cryns, R.J. Pennings, I. Walraven, G.M. Janssen, J.A. Maassen, B.F. Veldhuijzen, A.B. Arntzenius, D. Lindhout, C.W. Cremers, G. Van Camp, L.D. Dikkeschei, Molecular characterization of WFS1 in patients with Wolfram syndrome. J. Mol. Diagn. 5(2), 88–95 (2003)CrossRefGoogle Scholar
  22. 22.
    A. Colosimo, V. Guida, L. Rigoli, C. Di Bella, A. De Luca, S. Briuglia, L. Stuppia, D.C. Salpietro, B. Dallapiccola, Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. Hum. Mutat. 21(6), 622–629 (2003).  https://doi.org/10.1002/humu.10215 CrossRefPubMedGoogle Scholar
  23. 23.
    C.J. Smith, P.A. Crock, B.R. King, C.J. Meldrum, R.J. Scott, Phenotype-genotype correlations in a series of wolfram syndrome families. Diabetes Care 27(8), 2003–2009 (2004)CrossRefGoogle Scholar
  24. 24.
    F.M. Elli, S. Ghirardello, C. Giavoli, S. Gangi, L. Dioni, M. Crippa, P. Finelli, S. Bergamaschi, F. Mosca, A. Spada, P. Beck-Peccoz, A new structural rearrangement associated to Wolfram syndrome in a child with a partial phenotype. Gene 509(1), 168–172 (2012).  https://doi.org/10.1016/j.gene.2012.06.077 CrossRefPubMedGoogle Scholar
  25. 25.
    S.A. Yuca, N.D. Rendtorff, H. Boulahbel, M. Lodahl, L. Tranebjaerg, Y. Cesur, M. Dogan, C. Yilmaz, C. Akgun, M. Acikgoz, Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro). Eur. J. Med. Genet. 55(1), 37–42 (2012).  https://doi.org/10.1016/j.ejmg.2011.08.005 CrossRefPubMedGoogle Scholar
  26. 26.
    Aloi, C., Salina, A., Pasquali, L., Lugani, F., Perri, K., Russo, C., Tallone, R., Ghiggeri, G. M., Lorini, R., d’Annunzio, G., Wolfram syndrome: new mutations, different phenotype. PloS ONE 7(1) (2012).  https://doi.org/10.1371/journal.pone.0029150 CrossRefGoogle Scholar
  27. 27.
    M.A. Ganie, B.A. Laway, S. Nisar, M.M. Wani, M.L. Khurana, F. Ahmad, S. Ahmed, P. Gupta, I. Ali, I. Shabir, A. Shadan, A. Ahmed, S. Tufail, Presentation and clinical course of Wolfram (DIDMOAD) syndrome from North India. Diabet. Med. 28(11), 1337–1342 (2011).  https://doi.org/10.1111/j.1464-5491.2011.03377.x CrossRefPubMedGoogle Scholar
  28. 28.
    G. Yu, M.L. Yu, J.F. Wang, C.R. Gao, Z.J. Chen, WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures. Endocrine 38(2), 147–152 (2010).  https://doi.org/10.1007/s12020-010-9350-4 CrossRefPubMedGoogle Scholar
  29. 29.
    A. Zmyslowska, M. Borowiec, K. Antosik, M. Szalecki, A. Stefanski, B. Iwaniszewska, M. Jedrzejczyk, I. Pietrzak, W. Mlynarski, Wolfram syndrome in the Polish population: novel mutations and genotype-phenotype correlation. Clin. Endocrinol. 75(5), 636–641 (2011).  https://doi.org/10.1111/j.1365-2265.2011.04102.x CrossRefGoogle Scholar
  30. 30.
    M.U. Aluclu, M. Bahceci, A. Tuzcu, S. Arikan, D. Gokalp, A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for early appearance of clinical features of Wolfram syndrome and suicidal behaviour. Neuro Endocrinol. Lett. 27(6), 691–694 (2006)PubMedGoogle Scholar
  31. 31.
    F. Giuliano, S. Bannwarth, S. Monnot, A. Cano, B. Chabrol, B. Vialettes, B. Delobel, V. Paquis-Flucklinger, French Group of, W.S.: Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene. Hum. Mutat. 25(1), 99–100 (2005).  https://doi.org/10.1002/humu.9300 CrossRefPubMedGoogle Scholar
  32. 32.
    E. Domenech, M. Gomez-Zaera, V. Nunes, Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. Clin. Genet. 65(6), 463–469 (2004).  https://doi.org/10.1111/j.1399-0004.2004.00249.x CrossRefPubMedGoogle Scholar
  33. 33.
    P. Zalloua, S.T. Azar, M. Delepine, N.J. Makhoul, H. Blanc, M. Sanyoura, A. Lavergne, K. Stankov, A. Lemainque, P. Baz, C. Julier, WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. Hum. Mol. Genet. 17(24), 4012–4021 (2008).  https://doi.org/10.1093/hmg/ddn304 CrossRefPubMedGoogle Scholar
  34. 34.
    J.C. Zenteno, G. Ruiz, H.J. Perez-Cano, M. Camargo, Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations. Mol. Vis. 14(163), 1353–1357 (2008)PubMedPubMedCentralGoogle Scholar
  35. 35.
    M.R. Gasparin, F. Crispim, S.L. Paula, M.B. Freire, I.S. Dalbosco, T.D. Manna, J.E. Salles, F. Gasparin, A. Guedes, J.M. Marcantonio, M. Gambini, C.P. Salim, R.S. Moises, Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. Eur. J. Endocrinol. 160(2), 309–316 (2009).  https://doi.org/10.1530/EJE-08-0698 CrossRefPubMedGoogle Scholar
  36. 36.
    C. Hardy, F. Khanim, R. Torres, M. Scott-Brown, A. Seller, J. Poulton, D. Collier, J. Kirk, M. Polymeropoulos, F. Latif, T. Barrett, Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. Am. J. Hum. Genet. 65(5), 1279–1290 (1999).  https://doi.org/10.1086/302609 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Maryam Sobhani
    • 1
  • Mohammad Amin Tabatabaiefar
    • 2
    • 3
  • Soudeh Ghafouri-Fard
    • 4
  • Asadollah Rajab
    • 5
  • Sarah Mozafarpour
    • 6
  • Samaneh Nasrniya
    • 2
  • Abdol-Mohammad Kajbafzadeh
    • 6
  • Mohammad Reza Noori-Daloii
    • 7
    Email author
  1. 1.Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion MedicineTehranIran
  2. 2.Department of Genetics and Molecular Biology, School of MedicineIsfahan University of Medical SciencesIsfahanIran
  3. 3.Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable DiseaseIsfahan University of Medical SciencesIsfahanIran
  4. 4.Department of Medical GeneticsShahid Beheshti University of Medical SciencesTehranIran
  5. 5.Iranian Diabetes SocietyTehranIran
  6. 6.Department of UrologyMassachusetts General Hospital Harvard Medical SchoolBostonUSA
  7. 7.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran

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