Presence of a major WFS1 mutation in Spanish Wolfram Syndrome pedigrees

Montse Gómez-Zaera, Tim M. Strom, Benjamín Rodríguez, Xavier P. Estivill, Thomas Meitinger, Virginia Nunes

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disease mainly characterized by familial diabetes mellitus and optic atrophy. WS patients frequently present with other clinical features such as diabetes insipidus, renal abnormalities, psychiatric disorders, and a variety of neurologic symptoms: deafness, ataxia, peripheral neuropathy. A gene responsible for Wolfram Syndrome (WFS1) has been recently identified on chromosome 4p16.1. Twenty-two Wolfram patients from 16 Spanish families were screened for mutations in the WFS1 coding region by SSCP analysis and direct sequencing. Since WS has been considered a mitochondrial disorder for some time, mitochondrial DNA (mtDNA) in these families was also examined. WFS1 mutations were detected in 75% of families (12 of 16). One of these mutations, an insertion of 16 base pairs in exon 4, turned out to be notably frequent in Spanish pedigrees. As many as 50% of pedigrees with WFS1 mutations harbored this insertion, either in one (33% of cases) or in two chromosomes (67%). Ten other mutations were identified: 7 missense changes, 2 deletions, and 1 nonsense mutation. Only 3 of these changes had been previously described in non-Spanish pedigrees. Large mtDNA rearrangements and LHON point mutations were detected in four and six families, respectively. No correlation could be established between WFS1 gene mutations and specific point mutations or rearrangements in mtDNA. We would suggest first screening for the 16-bp insertion in exon 4 when a new Spanish WS case is reported.

Original languageEnglish
Pages (from-to)72-81
Number of pages10
JournalMolecular Genetics and Metabolism
Volume72
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Wolfram Syndrome
Tungsten
Pedigree
Mutation
Mitochondrial DNA
Insertional Mutagenesis
Point Mutation
Chromosomes
Medical problems
Exons
Optic Atrophy
Single-Stranded Conformational Polymorphism
Genes
Mitochondrial Diseases
Diabetes Insipidus
Neurodegenerative diseases
Gene Rearrangement
Nonsense Codon
Deafness
Peripheral Nervous System Diseases

Keywords

  • DIDMOAD
  • mtDNA deletions
  • mtDNA point mutations
  • WFS1 mutations
  • Wolfram syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Presence of a major WFS1 mutation in Spanish Wolfram Syndrome pedigrees. / Gómez-Zaera, Montse; Strom, Tim M.; Rodríguez, Benjamín; Estivill, Xavier P.; Meitinger, Thomas; Nunes, Virginia.

In: Molecular Genetics and Metabolism, Vol. 72, No. 1, 2001, p. 72-81.

Research output: Contribution to journalArticle

Gómez-Zaera, M, Strom, TM, Rodríguez, B, Estivill, XP, Meitinger, T & Nunes, V 2001, 'Presence of a major WFS1 mutation in Spanish Wolfram Syndrome pedigrees', Molecular Genetics and Metabolism, vol. 72, no. 1, pp. 72-81. https://doi.org/10.1006/mgme.2000.3107
Gómez-Zaera, Montse ; Strom, Tim M. ; Rodríguez, Benjamín ; Estivill, Xavier P. ; Meitinger, Thomas ; Nunes, Virginia. / Presence of a major WFS1 mutation in Spanish Wolfram Syndrome pedigrees. In: Molecular Genetics and Metabolism. 2001 ; Vol. 72, No. 1. pp. 72-81.
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