Journal article
Homozygosity Mapping Identifies an Additional Locus for Wolfram Syndrome on Chromosome 4q
American journal of human genetics, Vol.66(4), pp.1229-1236
2000
DOI: 10.1086/302858
PMCID: PMC1288190
PMID: 10739754
Abstract
Wolfram syndrome, which is sometimes referred to as “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal recessive neurodegenerative disorder for which only insulin-dependent diabetes mellitus and optic atrophy are necessary to make the diagnosis. Researchers have mapped Wolfram syndrome to chromosome 4p16.1, and, recently, a gene encoding a putative transmembrane protein has been cloned and mutations have been identified in patients. To pursue the possibility of locus heterogeneity, 16 patients from four different families were recruited. These patients, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported. There is an absence of diabetes insipidus in all affected family members. In addition, several patients have profound upper gastrointestinal ulceration and bleeding. With the use of three microsatellite markers (D4S432, D4S3023, and D4S2366) reported to be linked to the chromosome 4p16.1 locus, we significantly excluded linkage in three of the four families. The two affected individuals in one family showed homozygosity for all three markers from the region of linkage on chromosome 4p16.1. For the other three families, genetic heterogeneity for Wolfram syndrome was verified by demonstration of linkage to chromosome 4q22-24. In conclusion, we report the unique clinical findings and linkage-analysis results of 16 patients with Wolfram syndrome and provide further evidence for the genetic heterogeneity of this disorder. We also provide data on a new locus that plays a role in the etiology of insulin-dependent diabetes mellitus.
Details
- Title: Subtitle
- Homozygosity Mapping Identifies an Additional Locus for Wolfram Syndrome on Chromosome 4q
- Creators
- Hatem El-Shanti - Departments of Pediatrics and Medical Technology, School of Medicine, Jordan University of Science and Technology, Irbid, JordanAndrew C Lidral - Section of Orthodontics, College of Dentistry, Ohio State University, ColumbusNadim Jarrah - National Center for Diabetes, Endocrinology and Genetics, Amman, JordanLawrence Druhan - Section of Orthodontics, College of Dentistry, Ohio State University, ColumbusKamel Ajlouni - National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.66(4), pp.1229-1236
- Publisher
- Elsevier Inc
- DOI
- 10.1086/302858
- PMID
- 10739754
- PMCID
- PMC1288190
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 2000
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984093232102771
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