The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

Yi Yang; Afif Hentati; Han Xiang Deng; Omar Dabbagh; Toru Sasaki; Makito Hirano; Wu Yen Hung; Karim Ouahchi; Jianhua Yan; Anser C. Azim; Natalie Cole; Generoso Gascon; Ayesha Yagmour; Mongi Ben-Hamida; Margaret Pericak-Vance; Fayçal Hentati; Teepu Siddique

doi:10.1038/ng1001-160

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

Yi Yang, Afif Hentati, Han Xiang Deng, Omar Dabbagh, Toru Sasaki, Makito Hirano, Wu Yen Hung, Karim Ouahchi, Jianhua Yan, Anser C. Azim, Natalie Cole, Generoso Gascon, Ayesha Yagmour, Mongi Ben-Hamida, Margaret Pericak-Vance, Fayçal Hentati, Teepu Siddique

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

629 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

Original language	English (US)
Pages (from-to)	160-165
Number of pages	6
Journal	Nature genetics
Volume	29
Issue number	2
DOIs	https://doi.org/10.1038/ng1001-160
State	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Yang, Y., Hentati, A., Deng, H. X., Dabbagh, O., Sasaki, T., Hirano, M., Hung, W. Y., Ouahchi, K., Yan, J., Azim, A. C., Cole, N., Gascon, G., Yagmour, A., Ben-Hamida, M., Pericak-Vance, M., Hentati, F., & Siddique, T. (2001). The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nature genetics, 29(2), 160-165. https://doi.org/10.1038/ng1001-160

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. / Yang, Yi; Hentati, Afif; Deng, Han Xiang; Dabbagh, Omar; Sasaki, Toru; Hirano, Makito; Hung, Wu Yen; Ouahchi, Karim; Yan, Jianhua; Azim, Anser C.; Cole, Natalie; Gascon, Generoso; Yagmour, Ayesha; Ben-Hamida, Mongi; Pericak-Vance, Margaret; Hentati, Fayçal; Siddique, Teepu.

In: Nature genetics, Vol. 29, No. 2, 2001, p. 160-165.

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

Yang, Y, Hentati, A, Deng, HX, Dabbagh, O, Sasaki, T, Hirano, M, Hung, WY, Ouahchi, K, Yan, J, Azim, AC, Cole, N, Gascon, G, Yagmour, A, Ben-Hamida, M, Pericak-Vance, M, Hentati, F & Siddique, T 2001, 'The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis', Nature genetics, vol. 29, no. 2, pp. 160-165. https://doi.org/10.1038/ng1001-160

Yang, Yi ; Hentati, Afif ; Deng, Han Xiang ; Dabbagh, Omar ; Sasaki, Toru ; Hirano, Makito ; Hung, Wu Yen ; Ouahchi, Karim ; Yan, Jianhua ; Azim, Anser C. ; Cole, Natalie ; Gascon, Generoso ; Yagmour, Ayesha ; Ben-Hamida, Mongi ; Pericak-Vance, Margaret ; Hentati, Fayçal ; Siddique, Teepu. / The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. In: Nature genetics. 2001 ; Vol. 29, No. 2. pp. 160-165.

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title = "The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis",

abstract = "Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).",

author = "Yi Yang and Afif Hentati and Deng, {Han Xiang} and Omar Dabbagh and Toru Sasaki and Makito Hirano and Hung, {Wu Yen} and Karim Ouahchi and Jianhua Yan and Azim, {Anser C.} and Natalie Cole and Generoso Gascon and Ayesha Yagmour and Mongi Ben-Hamida and Margaret Pericak-Vance and Fay{\c c}al Hentati and Teepu Siddique",

note = "Funding Information: We are deeply indebted to the members of the Tunisian and Saudi Arabian families for their participation. This study was funded by grants from the NIH (PO1 NS21442, RO1 NS37912 and RO1 NS40308), the Les Turner ALS Foundation, Grant Healthcare Foundation, the Michael Jordan Foundation and the Ralph and Marian Falk Medical Research Trust. K.O. is a Muscular Dystrophy Association funded fellow and W.-Y.H. is a Muriel Heller Fellow.",

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AU - Dabbagh, Omar

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AU - Hirano, Makito

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AU - Ben-Hamida, Mongi

AU - Pericak-Vance, Margaret

AU - Hentati, Fayçal

AU - Siddique, Teepu

N1 - Funding Information: We are deeply indebted to the members of the Tunisian and Saudi Arabian families for their participation. This study was funded by grants from the NIH (PO1 NS21442, RO1 NS37912 and RO1 NS40308), the Les Turner ALS Foundation, Grant Healthcare Foundation, the Michael Jordan Foundation and the Ralph and Marian Falk Medical Research Trust. K.O. is a Muscular Dystrophy Association funded fellow and W.-Y.H. is a Muriel Heller Fellow.

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AB - Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

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The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

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