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Research reveals that cytidine deaminase gene mutation in association with the autosomal recessive form of hyper-IgM syndrome blocks IgG class switch recombination, IgG somatic hypermutations, and lymph node hyperplasia. Data indicate that cytidine deaminase is required for B cell terminal differentiation steps that confers affinity maturation of antibody responses.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Linkage analyses indicate that FHL is genetically heterogeneous and linked to 9q21.3-22, 10q21-22, or another as yet undefined locus. Sequencing of the coding regions of the perforin gene of eight unrelated 10q21-22-linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients. Cultured lymphocytes from patients had defective cytotoxic activity, and immunostaining revealed little or no perforin in the granules. Thus, defects in perforin are responsible for 10q21-22-[inked FHL Perforin-based effector systems are, therefore, involved not only in the lysis of abnormal cells but also in the down-regulation of cellular immune activation., FHL is a hemophagocytic lymphohistiocytic disorder in which previously healthy young children present with fever, splenomegaly, hepatomegaly, pancytopenia, coagulation abnormalities, neurological abnormalities, and high serum concentrations of interferon-[Gamma] (IFN-[Gamma]) and [...]

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Linkage analyses indicate that FHL is genetically heterogeneous and linked to 9q21.3-22,10q21-22, or another as yet undefined locus. Sequencing of the coding regions of the perforin gene of eight unrelated 10q21-22-linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients. Cultured lymphocytes from patients had defective cytotoxic activity, and immu-nostaining revealed little or no perforin in the granules. Thus, defects in perforin are responsible for 10q21-22-linked FHL Perforin-based effector systems are, therefore, involved not only in the lysis of abnormal cells but also in the down-regulation of cellular immune activation. [ABSTRACT FROM AUTHOR]

Examines the linkage of familial hemophagocytic lymphohistiocytosis (FHL) to 10q21-22. Characteristic of FHL; Relevance of T cell and marcophages on FHL; Correlation between neurological abnormalities and pancytopenia.