Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.
The American Journal of Human Genetics. 2001-11-01; 69(5): 1134-1140
DOI: 10.1086/323799
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1. Am J Hum Genet. 2001 Nov;69(5):1134-40. Epub 2001 Sep 20.
Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype
correlation.
Rodriguez D(1), 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.
Author information:
(1)Laboratoire de Neurogénétique Moléculaire, INSERM U546, Université Paris VI,
France.
Erratum in
Am J Hum Genet 2001 Dec;69(6):1413.
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.
DOI: 10.1086/323799
PMCID: PMC1274357
PMID: 11567214 [Indexed for MEDLINE]