Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4

Wolfram syndrome is an autosomal recessive disorder defined by the occurrence of diabetes mellitus and progressive bilateral optic atrophy. Wolfram syndrome homozygotes develop widespread nervous system abnormalities; in particular, they exhibit severe behavioural difficulties that often lead to suicide attempts or psychiatric hospitalizations. The Wolfram syndrome gene also predisposes heterozygous carriers to psychiatric disorders, and may contribute significantly to the overall burden of psychiatric illness. Based on a linkage analysis of 11 families segregating for this syndrome using microsatellite repeat polymorphisms throughout the human genome, we found the Wolfram syndrome gene to be linked to markers on the short arm of human chromosome 4, with Z_max = 6.46 at = 0.02 for marker D4S431.

1. Wolfram, D.J. & Wagener, H.P. Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Mayo Clin. Proc. 13, 715−718 (1938).
2. Shaw, D.A. & Duncan, L.J.P. Optic atrophy and nerve deafness in diabetes mellitus. J. Neurol. Neurosurg. Psychiat. 21, 47−49 (1958). | ISI | ChemPort |
3. Rorsman, G. & Soderstrom, N. Optic atrophy and juvenile diabetes mellitus with familial occurence. Acta Med. Scan. 182, 419−425 (1967). | ISI | ChemPort |
4. Rose, F.C., Fraser, G.R., Friedmann, A.I. & Kohner, E.M. The association of juvenile diabetes mellitus and optic atrophy: clinical and genetical aspects. Quart. J. Med. 35, 385−405 (1966). | PubMed  | ISI | ChemPort |
5. Ikkos, D.G., Fraser, G.R., Matsouki-Gavra, E. & Petrochilos, M. Association of juvenile diabetes mellitus, primary optic atrophy and perceptive hearing loss in three sibs, with additional idiopathic diabetes mellitus insipidus in one case. Acta Endocr. 65, 95 (1970). | PubMed  | ISI | ChemPort |
6. Page, M., Asmal, A.C. & Edwards, C.R.W. Recessive inheritance of diabetes: the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Quart. J. Med. 45, 505−520 (1976). | PubMed  | ISI | ChemPort |
7. Borgna-Pignatti, C., Marradi, P., Pinelli, L., Monetti, N. & Patrini, C. Thiamine-responsive anemia in DIDMOAD syndrome. J. Pediat. 114, 405−410 (1989). | PubMed  | ChemPort |
8. Swift, R.G., Sadler, D.B. & Swift, M. Psychiatric findings in Wolfram syndrome homozygotes. Lancet 336, 667−669 (1990). | Article | PubMed  | ISI | ChemPort |
9. Swift, R.G., Perkins, D.O., Chase, C.L., Sadler, D.B. & Swift, M. Physchiatric disorders in 36 families with Wolfram syndrome. Am. J. Psychiatry 148, 775−779 (1991). | PubMed  | ISI | ChemPort |
10. Rotig, A. et al. Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness. (Wolfram syndrome, MIM 222300). J. Clin. Invest. 91, 1095−1098 (1993). | PubMed  | ISI | ChemPort |
11. Swift, M., Kupper, L.L. & Chase, C.L. Effective testing of gene-disease associations. Am. J. hum. Genet. 47, 266−274 (1990). | PubMed  | ISI | ChemPort |
12. Gyapay, G. et al. The 1993−94 Généthon human genetic linkage map. Nature Genet. 7, 246−339 (1994). | Article | PubMed  | ISI | ChemPort |
13. Tagle, D.A., Blanchard-McQuate, K.L. & Collins, F.S. Dinucleotide repeat polymorphism in the Huntington's disease region at the D4S43 locus. Hum. molec. Genet. 1, 215 (1992). | PubMed  | ChemPort |
14. Polymeropoulos, M.H., Xiao, H., Torrey, E.F., DeLisi, L.E., Crow, T. & Merril, C.R. Search for a Genetic Event In Monozygotic Twins Discordant for Schizophrenia. Psychiatry Res. 48, 27−36 (1992). | Article | ISI |

	Top

	Top