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 language | English |
|---|---|
| Pages (from-to) | 1134-1140 |
| Number of pages | 7 |
| Journal | American Journal of Human Genetics |
| Volume | 69 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2001 |
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ASJC Scopus subject areas
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Infantile Alexander disease
T2 - Spectrum of GFAP mutations and genotype-phenotype correlation
AU - Rodriguez, D.
AU - Gauthier, F.
AU - Bertini, E.
AU - Bugiani, M.
AU - Brenner, M.
AU - N'Guyen, S.
AU - Goizet, C.
AU - Gelot, A.
AU - Surtees, R.
AU - Pedespan, J. M.
AU - Hernandorena, X.
AU - Troncoso, M.
AU - Uziel, G.
AU - Messing, A.
AU - Ponsot, G.
AU - Pham-Dinh, D.
AU - Dautigny, A.
AU - Boespflug-Tanguy, O.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034753242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034753242&partnerID=8YFLogxK
U2 - 10.1086/323799
DO - 10.1086/323799
M3 - Article
C2 - 11567214
AN - SCOPUS:0034753242
VL - 69
SP - 1134
EP - 1140
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -