Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome

Author(s):Show less -

Gasparin, Maria Regina R. ^[1] ; Crispim, Felipe ^[1] ; Paula, Silvia L. ^[2] ; Freire, Maria Beatriz S. ^[3] ; Dalbosco, Ivaldir S. ^[4] ; Della Manna, Thais ^[5] ; Salles, Joao Eduardo N. ^[6] ; Gasparin, Fabio ^[7] ; Guedes, Alexis ^[1] ; Marcantonio, Joao M. ; Gambini, Marcio ; Salim, Camila P. ^[1] ; Moises, Regina S. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Div Endocrinol, Sao Paulo - Brazil

^[2] Univ Fed Goias, Goiania, Go - Brazil

^[3] Med Sch Jundiai, Jundiai - Brazil

^[4] Univ Fdn Rio Grande, Rio Grande - Brazil

^[5] Univ Sao Paulo, Pediat Endocrinol Unit, Sao Paulo - Brazil

^[6] Med Sch Santa Casa Sao Paulo, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Dept Ophthalmol, Sao Paulo - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 160, n. 2, p. 309-316, FEB 2009.
• Web of Science Citations: 20

Abstract

Objective: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However. some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. Design and methods: Clinical characterization and analyses of the WFS1. gene were performed in 27 Brazilian patients with WS from 19 families. Results: We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea Conclusions: Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5. (AU)

• FAPESP's process: 05/01590-0 - Study of the WFS1 gene in Brazilian Wolfram syndrome families and phenotype-genotype correlations
• Grantee: Regina Celia Mello Santiago Moises
• Support Opportunities: Regular Research Grants