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

Hatem El-Shanti, Andrew C. Lidral, Nadim Jarrah, Lawrence Druhan, Kamel Ajlouni

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1229-1236
Number of pages8
JournalAmerican Journal of Human Genetics
Volume66
Issue number4
DOIs
Publication statusPublished - 2000
Externally publishedYes

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Wolfram Syndrome
Chromosomes
Genetic Heterogeneity
Type 1 Diabetes Mellitus
Optic Atrophy
Diabetes Insipidus
Inborn Genetic Diseases
Neurodegenerative Diseases
Microsatellite Repeats
Research Personnel
Hemorrhage
Phenotype
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Homozygosity mapping identifies additional locus for Wolfram syndrome on chromosome 4q. / El-Shanti, Hatem; Lidral, Andrew C.; Jarrah, Nadim; Druhan, Lawrence; Ajlouni, Kamel.

In: American Journal of Human Genetics, Vol. 66, No. 4, 2000, p. 1229-1236.

Research output: Contribution to journalArticle

El-Shanti, H, Lidral, AC, Jarrah, N, Druhan, L & Ajlouni, K 2000, 'Homozygosity mapping identifies additional locus for Wolfram syndrome on chromosome 4q', American Journal of Human Genetics, vol. 66, no. 4, pp. 1229-1236. https://doi.org/10.1086/302858
El-Shanti, Hatem ; Lidral, Andrew C. ; Jarrah, Nadim ; Druhan, Lawrence ; Ajlouni, Kamel. / Homozygosity mapping identifies additional locus for Wolfram syndrome on chromosome 4q. In: American Journal of Human Genetics. 2000 ; Vol. 66, No. 4. pp. 1229-1236.
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