Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain

Hans Gerd Nothwang, H. G. Kim, J. Aoki, M. Geisterfer, S. Kübart, R. D. Wegner, A. Van Moers, L. K. Ashworth, T. Haaf, J. Bell, H. Arai, N. Tommerup, H. H. Ropers, J. Wirth

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We report on the molecular characterization of a translocation t(1;19)(q21.3;q13.2) in a female with mental retardation, ataxia and atrophy of the brain. Sequence analysis of the breakpoints revealed an Alu-repeat-mediated mechanism of recombination that led to truncation of two genes: the kinase CLK2 and PAFAH1B3, the gene product of which interacts with LIS1 as part of a heterotrimeric G protein complex PAF-AH1B. In addition, two reciprocal fusion genes are present. One expressed fusion gene encodes the first 136 amino acids of PAFAH1B3 followed by the complete CLK2 protein. Truncated PAFAH1B3 protein lost its potential to interact with LIS1 whereas CLK2 activity was conserved within the fusion protein. These data emphasize the importance of PAF-AH1B in brain development and functioning and demonstrate the first fusion gene apparently not associated with cancer.

Original languageEnglish (US)
Pages (from-to)797-806
Number of pages10
JournalHuman Molecular Genetics
Volume10
Issue number8
StatePublished - Apr 1 2001

Fingerprint

Gene Fusion
Ataxia
Intellectual Disability
Atrophy
Brain
Heterotrimeric GTP-Binding Proteins
Proteins
Genetic Recombination
Genes
Sequence Analysis
Amino Acids
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Nothwang, H. G., Kim, H. G., Aoki, J., Geisterfer, M., Kübart, S., Wegner, R. D., ... Wirth, J. (2001). Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain. Human Molecular Genetics, 10(8), 797-806.

Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain. / Nothwang, Hans Gerd; Kim, H. G.; Aoki, J.; Geisterfer, M.; Kübart, S.; Wegner, R. D.; Van Moers, A.; Ashworth, L. K.; Haaf, T.; Bell, J.; Arai, H.; Tommerup, N.; Ropers, H. H.; Wirth, J.

In: Human Molecular Genetics, Vol. 10, No. 8, 01.04.2001, p. 797-806.

Research output: Contribution to journalArticle

Nothwang, HG, Kim, HG, Aoki, J, Geisterfer, M, Kübart, S, Wegner, RD, Van Moers, A, Ashworth, LK, Haaf, T, Bell, J, Arai, H, Tommerup, N, Ropers, HH & Wirth, J 2001, 'Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain', Human Molecular Genetics, vol. 10, no. 8, pp. 797-806.
Nothwang, Hans Gerd ; Kim, H. G. ; Aoki, J. ; Geisterfer, M. ; Kübart, S. ; Wegner, R. D. ; Van Moers, A. ; Ashworth, L. K. ; Haaf, T. ; Bell, J. ; Arai, H. ; Tommerup, N. ; Ropers, H. H. ; Wirth, J. / Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain. In: Human Molecular Genetics. 2001 ; Vol. 10, No. 8. pp. 797-806.
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abstract = "We report on the molecular characterization of a translocation t(1;19)(q21.3;q13.2) in a female with mental retardation, ataxia and atrophy of the brain. Sequence analysis of the breakpoints revealed an Alu-repeat-mediated mechanism of recombination that led to truncation of two genes: the kinase CLK2 and PAFAH1B3, the gene product of which interacts with LIS1 as part of a heterotrimeric G protein complex PAF-AH1B. In addition, two reciprocal fusion genes are present. One expressed fusion gene encodes the first 136 amino acids of PAFAH1B3 followed by the complete CLK2 protein. Truncated PAFAH1B3 protein lost its potential to interact with LIS1 whereas CLK2 activity was conserved within the fusion protein. These data emphasize the importance of PAF-AH1B in brain development and functioning and demonstrate the first fusion gene apparently not associated with cancer.",
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