A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)

Hiroshi Inoue; Yukio Tanizawa; Jon Wasson; Philip Behn; Kamini Kalidas; Ernesto Bernal-Mizrachi; Mike Mueckler; Helen Marshall; Helen Donis-Keller; Patricia Crock; Douglas Rogers; Masahiko Mikuni; Hisashi Kumashiro; Koichiro Higashi; Gen Sobue; Yoshitomo Oka; M. Alan Permutt

doi:10.1038/2441

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)

Hiroshi Inoue, Yukio Tanizawa, Jon Wasson, Philip Behn, Kamini Kalidas, Ernesto Bernal-Mizrachi, Mike Mueckler, Helen Marshall, Helen Donis-Keller, Patricia Crock, Douglas Rogers, Masahiko Mikuni, Hisashi Kumashiro, Koichiro Higashi, Gen Sobue, Yoshitomo Oka, M. Alan Permutt

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Abstract

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin- dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplo-types, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet β-cells and neurons.

Original language	English (US)
Pages (from-to)	143-148
Number of pages	6
Journal	Nature genetics
Volume	20
Issue number	2
DOIs	https://doi.org/10.1038/2441
State	Published - 1998
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Mueckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., & Alan Permutt, M. (1998). A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nature genetics, 20(2), 143-148. https://doi.org/10.1038/2441

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). / Inoue, Hiroshi; Tanizawa, Yukio; Wasson, Jon; Behn, Philip; Kalidas, Kamini; Bernal-Mizrachi, Ernesto; Mueckler, Mike; Marshall, Helen; Donis-Keller, Helen; Crock, Patricia; Rogers, Douglas; Mikuni, Masahiko; Kumashiro, Hisashi; Higashi, Koichiro; Sobue, Gen; Oka, Yoshitomo; Alan Permutt, M.

In: Nature genetics, Vol. 20, No. 2, 1998, p. 143-148.

Research output: Contribution to journal › Article › peer-review

Inoue, H, Tanizawa, Y, Wasson, J, Behn, P, Kalidas, K, Bernal-Mizrachi, E, Mueckler, M, Marshall, H, Donis-Keller, H, Crock, P, Rogers, D, Mikuni, M, Kumashiro, H, Higashi, K, Sobue, G, Oka, Y & Alan Permutt, M 1998, 'A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)', Nature genetics, vol. 20, no. 2, pp. 143-148. https://doi.org/10.1038/2441

Inoue, Hiroshi ; Tanizawa, Yukio ; Wasson, Jon ; Behn, Philip ; Kalidas, Kamini ; Bernal-Mizrachi, Ernesto ; Mueckler, Mike ; Marshall, Helen ; Donis-Keller, Helen ; Crock, Patricia ; Rogers, Douglas ; Mikuni, Masahiko ; Kumashiro, Hisashi ; Higashi, Koichiro ; Sobue, Gen ; Oka, Yoshitomo ; Alan Permutt, M. / A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). In: Nature genetics. 1998 ; Vol. 20, No. 2. pp. 143-148.

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title = "A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)",

abstract = "Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin- dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplo-types, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet β-cells and neurons.",

author = "Hiroshi Inoue and Yukio Tanizawa and Jon Wasson and Philip Behn and Kamini Kalidas and Ernesto Bernal-Mizrachi and Mike Mueckler and Helen Marshall and Helen Donis-Keller and Patricia Crock and Douglas Rogers and Masahiko Mikuni and Hisashi Kumashiro and Koichiro Higashi and Gen Sobue and Yoshitomo Oka and {Alan Permutt}, M.",

note = "Funding Information: We are grateful to the patients, their families and physicians for participating in this study. We acknowledge S. Nanko, T. Ikeuchi, K. Yamamoto, Y. Hoshino, H.Yokoyama, S. Hoshino, S. Niwa and N. Nakao for care of patients, compiling clinical data and obtaining patient samples. The authors thank Y. Kora, Y. Mizukami, C. Welling, B. Wilson and C. Iannotti for technical assistance, and J. Wokurka for preparation of the manuscript. We also thank J. Rice for initial help with power calculations for linkage analysis, P. Goodfellow for helpful advice throughout the project and C. Helms for construction of the meiotic map of chromosome 4p. S. Chissoe, R. Wilson and E. Mardis gave guidance with the shotgun sequencing. This work was supported in part by NIH grants DK16746 and DK20579 (M.A.P.), DK07120 (P.B.), HG00100 (H.D.-K.), and DK38494 (M.M.), Grant-in-Aid for Creative Basic Research (10NP0201) from the Ministry of Education, Science, Sports and Culture of Japan (Y.O.), Grants-in-Aid for Scientific Research (10671074) from the Ministry of Education, Science, Sports and Culture of Japan (Y.T.) and a Mentor-Based Fellowship Award from the American Diabetes Association (Y.T., H.I.).",

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AU - Inoue, Hiroshi

AU - Tanizawa, Yukio

AU - Wasson, Jon

AU - Behn, Philip

AU - Kalidas, Kamini

AU - Bernal-Mizrachi, Ernesto

AU - Mueckler, Mike

AU - Marshall, Helen

AU - Donis-Keller, Helen

AU - Crock, Patricia

AU - Rogers, Douglas

AU - Mikuni, Masahiko

AU - Kumashiro, Hisashi

AU - Higashi, Koichiro

AU - Sobue, Gen

AU - Oka, Yoshitomo

AU - Alan Permutt, M.

N1 - Funding Information: We are grateful to the patients, their families and physicians for participating in this study. We acknowledge S. Nanko, T. Ikeuchi, K. Yamamoto, Y. Hoshino, H.Yokoyama, S. Hoshino, S. Niwa and N. Nakao for care of patients, compiling clinical data and obtaining patient samples. The authors thank Y. Kora, Y. Mizukami, C. Welling, B. Wilson and C. Iannotti for technical assistance, and J. Wokurka for preparation of the manuscript. We also thank J. Rice for initial help with power calculations for linkage analysis, P. Goodfellow for helpful advice throughout the project and C. Helms for construction of the meiotic map of chromosome 4p. S. Chissoe, R. Wilson and E. Mardis gave guidance with the shotgun sequencing. This work was supported in part by NIH grants DK16746 and DK20579 (M.A.P.), DK07120 (P.B.), HG00100 (H.D.-K.), and DK38494 (M.M.), Grant-in-Aid for Creative Basic Research (10NP0201) from the Ministry of Education, Science, Sports and Culture of Japan (Y.O.), Grants-in-Aid for Scientific Research (10671074) from the Ministry of Education, Science, Sports and Culture of Japan (Y.T.) and a Mentor-Based Fellowship Award from the American Diabetes Association (Y.T., H.I.).

PY - 1998

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AB - Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin- dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplo-types, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet β-cells and neurons.

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ER -

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)

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