Abstract
Wolfram syndrome is a rare hereditary disease characterized by diabetes mellitus and optic atrophy. The outcome of this disease is always poor. WFS1 gene mutation is the main cause of this disease. A patient with diabetes mellitus, diabetes insipidus, renal tract disorder, psychiatric abnormality, and cataract was diagnosed with Wolfram syndrome. Mutations in open reading frame (ORF) of WFS1 gene was analyzed by sequencing. Mutations in WFS1 gene was also summarized by a systematic review in Pubmed and Chinese biological and medical database. Sequencing of WFS1 gene in this patient showed a new mutation, 1962G>A, and two other non-sense mutations, 2433A>G and 2565G>A. Systematic review included 219 patients in total and identified 172 WFS1 gene mutations, most of which were located in Exon 8. These mutations in WFS1 gene might be useful in prenatal diagnosis of Wolfram syndrome.
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T.G. Barrett, S.E. Bundey, A.F. Macleod, Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 345, 1458–1463 (1995)
B.T. Kinsley, M. Swift, R.H. Dumont et al., Morbidity and mortality in the Wolfram syndrome. Diabetes Care 18, 1566–1570 (1995)
D.J. Wolfram, H.P. Wagener, Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Mayo Clin. Proc. 13, 715–718 (1938)
S. Hofmann, C. Philbrook, K.D. Gerbitz et al., Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product. Hum. Mol. Genet. 12, 2003–2012 (2003)
A. Barrientos, V. Volpini, J. Casademont et al., A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome. J. Clin. Invest. 97, 1570–1576 (1996)
J. Hong, Y.W. Zhang, H.J. Zhang et al., The novel compound heterozygous mutations, V434del and W666X, in WFS1 gene causing the Wolfram syndrome in a Chinese family. Endocrine 35, 151–157 (2009)
F. Lombardo, P. Chiurazzi, K. Hörtnagel et al., Clinical picture, evolution and peculiar molecular findings in a very large pedigree with Wolfram syndrome. J. Pediatr. Endocrinol. Metab. 18, 1391–1397 (2005)
M.U. Aluclu, M. Bahceci, A. Tuzcu et al., 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, 691–694 (2006)
A. Cano, C. Rouzier, S. Monnot et al., Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. Am. J. Med. Genet. A 143A, 1605–1612 (2007)
A. Colosimo, V. Guida, L. Rigoli et al., Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. Hum. Mutat. 21, 622–629 (2003)
E. Domènech, M. Gómez-Zaera, V. Nunes, Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. Clin. Genet. 65, 463–469 (2004)
P.B. Eller, B. Foger, R. Gander et al., Wolfram syndrome: a clinical and molecular genetic analysis. J. Med. Genet. 38, E37 (2001)
Q.C. Fang, W.P. Jia, R. Zhang et al., A novel mutation of WFS1 gene in Chinese patients with Wolfram syndrome. Zhonghua Yi Xue Za Zhi 85, 2468–2471 (2005)
M.R. Gasparin, F. Crispim, S.L. Paula et al., Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. Eur. J. Endocrinol. 160, 309–316 (2009)
F. Giuliano, S. Bannwarth, S. Monnot et al., Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene. Hum. Mutat. 25, 99–100 (2005)
M. Gomez-Zaera, T.M. Strom, B. Rodriguez et al., Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. Mol. Genet. Metab. 72, 72–81 (2001)
L. Hansen, H. Eiberg, T. Barrett et al., Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. Eur. J. Hum. Genet. 13, 1275–1284 (2005)
C. Hardy, F. Khanim, R. Torres et al., Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. Am. J. Hum. Genet. 65, 1279–1290 (1999)
H. Inoue, Y. Tanizawa, J. Wasson et al., A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat. Genet. 20, 143–148 (1998)
K. Inukai, T. Awata, K. Inoue et al., Identification of a novel WFS1 mutation (AFF344–345ins) in Japanese patients with Wolfram syndrome. Diabetes Res. Clin. Pract. 69, 136–141 (2005)
A. Kadayifci, Y. Kepekci, Y. Coskun et al., Wolfram syndrome in a family with variable expression. Acta Medica. 44, 115–118 (2001)
A. Nakamura, C. Shimizu, S. Nagai et al., A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive diabetes-related antibodies. Diabetes Res. Clin. Pract. 73, 215–217 (2006)
W. Sam, H. Qin, B. Crawford et al., Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. Clin. Genet. 59, 136–138 (2001)
S.G. Shu, C.R. Tsai, C.S. Chi, Wolfram syndrome: phenotype and novel mutation in two Taiwanese siblings. J. Formos. Med. Assoc. 102, 808–811 (2003)
C.J. Smith, P.A. Crock, B.R. King et al., Phenotype-genotype correlations in a series of wolfram syndrome families. Diabetes Care 27, 2003–2009 (2004)
T.M. Strom, K. Hortnagel, S. Hofmann et al., 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, 2021–2028 (1998)
A. Tessa, I. Carbone, M.C. Matteoli et al., Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. Hum. Mutat. 17, 348–349 (2001)
J.M. van ven Ouweland, K. Cryns, R.J. Pennings et al., Molecular characterization of WFS1 in patients with Wolfram syndrome. J. Mol. Diagn. 5, 88–95 (2003)
J.C. Zenteno, G. Ruiz, H.J. Pérez-Cano et al., Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations. Mol. Vis. 14, 1353–1357 (2008)
T.G. Barrett, S.E. Bundey, Wolfram (DIDMOAD) syndrome. J. Med. Genet. 34, 838–841 (1997)
S. Ito, R. Sakakibara, T. Hattori, Wolfram syndrome presenting marked brain mr imaging abnormalities with few neurologic abnormalities. Am. J. Neuroradiol. 28, 305–306 (2007)
E. Domenech, H. Kruyer, C. Gomez et al., First prenatal diagnosis for Wolfram syndrome by molecular analysis of the WFS1 gene. Prenat. Diagn. 24, 787–789 (2004)
A.A. Osman, M. Saito, C. Makepeace et al., Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium. J. Biol. Chem. 278, 52755–55262 (2003)
S. Amr, C. Heisey, M. Zhang et al., A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am. J. Hum. Genet. 81, 673–683 (2007)
Y.F. Chen, C.H. Kao, Y.T. Chen et al., Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 23, 1183–1194 (2009)
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G. Yu and M. Yu contributed equally to this article.
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Yu, G., Yu, Ml., Wang, Jf. et al. WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures. Endocr 38, 147–152 (2010). https://doi.org/10.1007/s12020-010-9350-4
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DOI: https://doi.org/10.1007/s12020-010-9350-4