Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q

Citation
H. El-shanti et al., Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q, AM J HU GEN, 66(4), 2000, pp. 1229-1236
Citations number
42
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Journal title
AMERICAN JOURNAL OF HUMAN GENETICS
ISSN journal
00029297 → ACNP
Volume
66
Issue
4
Year of publication
2000
Pages
1229 - 1236
Database
ISI
SICI code
0002-9297(200004)66:4<1229:HMIAAL>2.0.ZU;2-5
Abstract
Wolfram syndrome, which is sometimes referred to as "DIDMOAD" (diabetes ins ipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal re cessive neurodegenerative disorder for which only insulin-dependent diabete s mellitus and optic atrophy are necessary to make the diagnosis. Researche rs have mapped Wolfram syndrome to chromosome 4p16.1, and, recently, a gene encoding a putative transmembrane protein has been cloned and mutations ha ve been identified in patients. To pursue the possibility of locus heteroge neity, 16 patients from four different families were recruited. These patie nts, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported. There is an absence of diabetes in sipidus in all affected family members. In addition, several patients have profound upper gastrointestinal ulceration and bleeding. With the use of th ree microsatellite markers (D4S432, D4S3023, and D4S2366) reported to be li nked to the chromosome 4p16.1 locus, we significantly excluded linkage in t hree of the fear families. The two affected individuals in one family showe d homozygosity for all three markers from the region of linkage on chromoso me 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 re sults 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 melli tus.