Follow-up study of 22 Chinese children with Alexander disease and analysis of parental origin of de novo GFAP mutations.

[alexander disease]

To delineate the phenotype and genotype in Chinese children with type I Alexander disease (AxD ) and the parental origin of de novo glial fibrillary acidic protein (GFAP ) mutations . Twenty -two children with clinically diagnosed type I AxD were followed up for 1 .66 -6 .62 years . Allele-specific PCR was used for the analysis of parental origin of the allele harboring the de novo mutation . Phenotype of these patients were consistent with type I AxD described in other population , with developmental delay (motor delay in 81 .82 %, cognitive delay in 63 .64 %), macrocephaly (100 %), seizures (95 .45 %), paroxysmal deterioration (27 .27 %) and typical brain magnetic resonance imaging (100 %). Progression was slower than reported . At 8 .55 years of age (5 .29 -13 .25 ), all patients who underwent the second follow-up were alive . Eleven heterozygous missense mutations of GFAP were identified in 21 patients , with three novel mutations . Reported hot spot mutations , p .R 79 , p .R 239 and p .R 88 , were also identified in Chinese patients . Mutations were de novo in all but one case . The mother of a proband was demonstrated to be a presymptomatic patient with type II AxD with a p .R 79 H mutation . Ninety percent of de novo mutations were on the paternal allele demonstrated by allele-specific PCR . This is the largest follow-up study on Chinese children with AxD . The phenotypes of these patients are consistent with reports in other populations . GFAP mutations were identified in 95 .46 % of Chinese children with clinically diagnosed type I AxD . Our data suggested a male germ-line transmission .

Diseases
Validation

Diseases presenting "cognitive delay" symptom

alexander disease

pyruvate dehydrogenase deficiency

This symptom has already been validated