Premium
Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic omani patients
Author(s) -
Muralitharan Shanmugakonar,
Wali Yasser A.,
Dennison David,
Lamki Zakia A.,
Zachariah Mathew,
Nagwa El Banna,
Pathare Anil,
Krishnamoorthy Rajagopal
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21009
Subject(s) - perforin , hemophagocytic lymphohistiocytosis , hepatosplenomegaly , immunology , pancytopenia , hypofibrinogenemia , missense mutation , medicine , gene , biology , genetics , cd8 , mutation , immune system , pathology , disease , bone marrow , fibrinogen
Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive immune disorder, characterized by fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, markedly elevated levels of inflammatory cytokines, and impaired cytotoxic activity of lymphocytes. FHL is often fatal in early infancy. Histologic features include organ infiltration by activated macrophages and lymphocytes. Four genetic loci (FHL1, 2, 3, and 4) have been identified, of which FHL2 involves mutations in the perforin gene and is present in 20–50% of patients with FHL. We herein report the first comprehensive molecular analysis of 16 unrelated cases of FHL in ethnic Omanis. Using direct DNA sequencing analysis in 11 families, seven different mutations were identified in the coding region of the perforin gene, of which five were novel. Perforin gene defects do not seem to be involved in one‐third of the cases of FHL in ethnic Omanis. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.