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Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations

PURPOSE: To describe the first instance of genotyping in a Latin American family with Wolfram syndrome (WS). METHODS: Four affected siblings and their healthy parents were studied. Ophthalmologic examination included best corrected visual acuity determination, funduscopy, fluorescein retinal angiogr...

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Autores principales: Zenteno, Juan Carlos, Ruiz, Gabriela, Pérez-Cano, Hector J., Camargo, Mayra
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483297/
https://www.ncbi.nlm.nih.gov/pubmed/18660851
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author Zenteno, Juan Carlos
Ruiz, Gabriela
Pérez-Cano, Hector J.
Camargo, Mayra
author_facet Zenteno, Juan Carlos
Ruiz, Gabriela
Pérez-Cano, Hector J.
Camargo, Mayra
author_sort Zenteno, Juan Carlos
collection PubMed
description PURPOSE: To describe the first instance of genotyping in a Latin American family with Wolfram syndrome (WS). METHODS: Four affected siblings and their healthy parents were studied. Ophthalmologic examination included best corrected visual acuity determination, funduscopy, fluorescein retinal angiography, and Goldmann kinetic perimetry. Molecular methods included linkage analysis using microsatellites markers located on the markers located on the Wofram syndrome 1 (WFS1) region at 4p16.1, PCR amplification and direct nucleotide sequencing analysis of the complete coding region and exon/intron junctions of WFS1. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous frameshift mutation. RESULTS: The four affected siblings presented with a homogeneous clinical picture characterized by early onset diabetes mellitus, severe optic atrophy, and progressive hearing loss. Linkage analysis indicated that all four sibs were heterozygous for markers linked to the WFS1 region and that each inherited the same allele from the mother and the same from the father, suggesting compound heterozygosity. Direct WFS1 analysis disclosed a paternally inherited novel missense R177P mutation whereas allele-specific cloning and sequencing revealed a novel WFS1 16 bp deletion that was inherited from the mother. CONCLUSIONS: Our report of two novel WFS1 mutations expands the molecular spectrum of Wolfram syndrome. This is the first documented case of the molecular basis of the disease in a Latin American family. Analysis of more patients from this population will establish if compound heterozygosity is commonly found in affected individuals from this ethnic group.
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spelling pubmed-24832972008-07-25 Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations Zenteno, Juan Carlos Ruiz, Gabriela Pérez-Cano, Hector J. Camargo, Mayra Mol Vis Research Article PURPOSE: To describe the first instance of genotyping in a Latin American family with Wolfram syndrome (WS). METHODS: Four affected siblings and their healthy parents were studied. Ophthalmologic examination included best corrected visual acuity determination, funduscopy, fluorescein retinal angiography, and Goldmann kinetic perimetry. Molecular methods included linkage analysis using microsatellites markers located on the markers located on the Wofram syndrome 1 (WFS1) region at 4p16.1, PCR amplification and direct nucleotide sequencing analysis of the complete coding region and exon/intron junctions of WFS1. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous frameshift mutation. RESULTS: The four affected siblings presented with a homogeneous clinical picture characterized by early onset diabetes mellitus, severe optic atrophy, and progressive hearing loss. Linkage analysis indicated that all four sibs were heterozygous for markers linked to the WFS1 region and that each inherited the same allele from the mother and the same from the father, suggesting compound heterozygosity. Direct WFS1 analysis disclosed a paternally inherited novel missense R177P mutation whereas allele-specific cloning and sequencing revealed a novel WFS1 16 bp deletion that was inherited from the mother. CONCLUSIONS: Our report of two novel WFS1 mutations expands the molecular spectrum of Wolfram syndrome. This is the first documented case of the molecular basis of the disease in a Latin American family. Analysis of more patients from this population will establish if compound heterozygosity is commonly found in affected individuals from this ethnic group. Molecular Vision 2008-07-25 /pmc/articles/PMC2483297/ /pubmed/18660851 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zenteno, Juan Carlos
Ruiz, Gabriela
Pérez-Cano, Hector J.
Camargo, Mayra
Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title_full Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title_fullStr Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title_full_unstemmed Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title_short Familial Wolfram syndrome due to compound heterozygosity for two novel WFS1 mutations
title_sort familial wolfram syndrome due to compound heterozygosity for two novel wfs1 mutations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483297/
https://www.ncbi.nlm.nih.gov/pubmed/18660851
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