Journal article
A Homozygous Mutation in a Novel Zinc-Finger Protein, ERIS, Is Responsible for Wolfram Syndrome 2
American journal of human genetics, Vol.81(4), pp.673-683
2007
DOI: 10.1086/520961
PMCID: PMC2227919
PMID: 17846994
Abstract
A single missense mutation was identified in a novel, highly conserved zinc-finger gene,
ZCD2, in three consanguineous families of Jordanian descent with Wolfram syndrome (WFS). It had been shown that these families did not have mutations in the WFS1 gene (
WFS1) but were mapped to the WFS2 locus at 4q22-25. A G→C transversion at nucleotide 109 predicts an amino acid change from glutamic acid to glutamine (E37Q). Although the amino acid is conserved and the mutation is nonsynonymous, the pathogenesis for the disorder is because the mutation also causes aberrant splicing. The mutation was found to disrupt messenger RNA splicing by eliminating exon 2, and it results in the introduction of a premature stop codon. Mutations in
WFS1 have also been found to cause low-frequency nonsyndromic hearing loss, progressive hearing loss, and isolated optic atrophy associated with hearing loss. Screening of 377 probands with hearing loss did not identify mutations in the WFS2 gene. The
WFS1-encoded protein, Wolframin, is known to localize to the endoplasmic reticulum and plays a role in calcium homeostasis. The
ZCD2-encoded protein, ERIS (
endoplasmic
reticulum
intermembrane
small protein), is also shown to localize to the endoplasmic reticulum but does not interact directly with Wolframin. Lymphoblastoid cells from affected individuals show a significantly greater rise in intracellular calcium when stimulated with thapsigargin, compared with controls, although no difference was observed in resting concentrations of intracellular calcium.
Details
- Title: Subtitle
- A Homozygous Mutation in a Novel Zinc-Finger Protein, ERIS, Is Responsible for Wolfram Syndrome 2
- Creators
- Sami Amr - From the Departments of Human Genetics, Virginia Commonwealth University, RichmondCindy Heisey - From the Departments of Human Genetics, Virginia Commonwealth University, RichmondMin Zhang - Pharmacology and Toxicology, Virginia Commonwealth University, RichmondXia-Juan Xia - From the Departments of Human Genetics, Virginia Commonwealth University, RichmondKathryn H Shows - From the Departments of Human Genetics, Virginia Commonwealth University, RichmondKamel Ajlouni - Department of Internal Medicine, Jordan University Hospital, Amman, JordanArti Pandya - From the Departments of Human Genetics, Virginia Commonwealth University, RichmondLeslie S Satin - Pharmacology and Toxicology, Virginia Commonwealth University, RichmondHatem El-Shanti - National Center for Diabetes, Endocrinology, and Genetics, Amman, JordanRita Shiang - From the Departments of Human Genetics, Virginia Commonwealth University, Richmond
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.81(4), pp.673-683
- Publisher
- Elsevier Inc
- DOI
- 10.1086/520961
- PMID
- 17846994
- PMCID
- PMC2227919
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 2007
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984093230802771
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