Infantile Alexander disease: Spectrum of GFAP mutations and genotype-phenotype correlation

D. Rodriguez, F. Gauthier, E. Bertini, M. Bugiani, M. Brenner, S. N'Guyen, C. Goizet, A. Gelot, R. Surtees, J. M. Pedespan, X. Hernandorena, M. Troncoso, G. Uziel, A. Messing, G. Ponsot, D. Pham-Dinh, A. Dautigny, O. Boespflug-Tanguy

Research output: Contribution to journalArticle

Abstract

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

Original languageEnglish
Pages (from-to)1134-1140
Number of pages7
JournalAmerican Journal of Human Genetics
Volume69
Issue number5
DOIs
Publication statusPublished - 2001

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Alexander Disease
Glial Fibrillary Acidic Protein
Genetic Association Studies
Mutation
Arginine
Megalencephaly
Mosaicism
Prenatal Diagnosis
Neuroimaging
Exons
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Rodriguez, D., Gauthier, F., Bertini, E., Bugiani, M., Brenner, M., N'Guyen, S., ... Boespflug-Tanguy, O. (2001). Infantile Alexander disease: Spectrum of GFAP mutations and genotype-phenotype correlation. American Journal of Human Genetics, 69(5), 1134-1140. https://doi.org/10.1086/323799

Infantile Alexander disease : Spectrum of GFAP mutations and genotype-phenotype correlation. / Rodriguez, D.; Gauthier, F.; Bertini, E.; Bugiani, M.; Brenner, M.; N'Guyen, S.; Goizet, C.; Gelot, A.; Surtees, R.; Pedespan, J. M.; Hernandorena, X.; Troncoso, M.; Uziel, G.; Messing, A.; Ponsot, G.; Pham-Dinh, D.; Dautigny, A.; Boespflug-Tanguy, O.

In: American Journal of Human Genetics, Vol. 69, No. 5, 2001, p. 1134-1140.

Research output: Contribution to journalArticle

Rodriguez, D, Gauthier, F, Bertini, E, Bugiani, M, Brenner, M, N'Guyen, S, Goizet, C, Gelot, A, Surtees, R, Pedespan, JM, Hernandorena, X, Troncoso, M, Uziel, G, Messing, A, Ponsot, G, Pham-Dinh, D, Dautigny, A & Boespflug-Tanguy, O 2001, 'Infantile Alexander disease: Spectrum of GFAP mutations and genotype-phenotype correlation', American Journal of Human Genetics, vol. 69, no. 5, pp. 1134-1140. https://doi.org/10.1086/323799
Rodriguez, D. ; Gauthier, F. ; Bertini, E. ; Bugiani, M. ; Brenner, M. ; N'Guyen, S. ; Goizet, C. ; Gelot, A. ; Surtees, R. ; Pedespan, J. M. ; Hernandorena, X. ; Troncoso, M. ; Uziel, G. ; Messing, A. ; Ponsot, G. ; Pham-Dinh, D. ; Dautigny, A. ; Boespflug-Tanguy, O. / Infantile Alexander disease : Spectrum of GFAP mutations and genotype-phenotype correlation. In: American Journal of Human Genetics. 2001 ; Vol. 69, No. 5. pp. 1134-1140.
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