Establishment and characterization of an atypical cell line from a patient with Wiskott-Aldrich-Syndrome and bone marrow allografting

Se aislaron blastos atípicos de la sangre periférica de un niño con síndrome de Wiskott-Aldrich y autotransplante de médula ósea. Las células fueron inmunotipificadas como monoblastos y crecieron en cultivo tisular en doble tiempo de 3 a 4 días. Las células aisladas originalmente y los cultivos iniciales, contenían antígenos tanto del virus herpes humano-6 (HHV-6) como del virus herpes humano-7 (HHV-7) y ácido desoxirribonucleico (ADN). Lo que disminuyó con la desdiferenciación celular en los cultivos subsecuentes. Los sobrenadantes de los cultivos celulares contenían cantidades moderadas de interleucina-6 (IL-6) y marcados niveles de factor estimulante de colonias-granulocito-monocítico (GM-CSF). Se discutió el caso desde el punto de vista de una posible co-patogénesis viral

Wiskott-Aldrich syndrome in a family with Fanconi anemia.

Thrombocytopenia may be the presenting finding for both Wiskott-Aldrich syndrome and Fanconi anemia. We examined a sibship of four boys who had features of both of these hematologic disorders. Peripheral blood lymphocytes from three of the boys demonstrated DNA instability when cultured with diepoxybutane, confirming the diagnosis of Fanconi anemia in these patients. However, results of linkage analysis and X chromosome inactivation studies were consistent with the diagnosis of Wiskott-Aldrich syndrome in two of the boys, including one of the boys with Fanconi anemia. These findings could be attributed to the occurrence of two rare genetic disorders in a single family or to an unusual variant of Fanconi anemia. The recent identification of the Wiskott-Aldrich gene permitted us to address this question directly. Epstein-Barr virus-transformed cell lines from the two boys thought to have Wiskott-Aldrich syndrome on the basis of linkage analysis failed to express transcripts for the Wiskott-Aldrich gene. Genomic DNA from these two patients demonstrated a G insertion in the tenth exon of the Wiskott-Aldrich gene, resulting in a frameshift and a premature stop codon. Surprisingly, the patient with Fanconi anemia and a null mutation in the Wiskott-Aldrich gene had typical Fanconi anemia but mild Wiskott-Aldrich syndrome.

A prenatal study of fetal platelet count and size with application to fetus at risk for Wiskott-Aldrich syndrome.

Platelet counts and platelet size were determined in midtrimester fetuses to obtain reference values to be used in prenatal diagnosis of inheritable platelet disorders. In 17- to 21-week fetuses, platelet counts ranged between 135 and 283 x 10(9)/L, and thus did not differ from those of newborn infants and adults. Mean platelet volume fell between 6.0 and 7.0 fl, which is in the range for adults. The data were used to exclude Wiskott-Aldrich syndrome in an 18-week fetus at 50% risk of being affected.