Archetypal and new families with Alexander disease and novel mutations in GFAP.

[alexander disease]

To describe genetic analyses of the 2 most thoroughly studied , historically seminal multigenerational families with Alexander disease described prior to the identification of GFAP as the related gene , as well as 1 newly discovered family .Clinical histories were obtained and DNA was analyzed from blood , cheek epithelial cells , or fixed paraffin-embedded surgical samples .Affected and unaffected adult members of 3 families and affected children were included .Mutations in GFAP and behavior of mutant protein in cellular transfection assays .Family A contains 4 siblings in whom we found a novel p .Ser 247 P ro mutation that was paternally inherited . The phenotypes of these siblings include 1 unaffected adult , 1 individual with juvenile -onset disease , and 2 individuals with adult-onset disease . Family B spans 4 generations , including the first described patient with adult-onset disease originally reported in 1968 . Analysis of members of the later generations revealed a novel p .Asp 417 A la mutation . Family C contains 3 generations . We detected a novel p .Gln 426 L eu mutation that , to our knowledge , is the farthest C-terminal mutation known .These families display clear evidence of variable phenotypes but do not support recessive inheritance . While germline mosaicism can not be excluded for 1 family (A ), we propose that for genetic counseling purposes the risk of germline mosaicism should be described as less than 1 %.

Diseases
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Diseases presenting "p.asp417ala mutation" symptom

alexander disease

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