Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic Omani patients.
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.
Department of Child Health, Sultan Qaboos University Hospital, Al-Khoud, Oman.
Shanmugakonar
S
Muralitharan
Yasser A
YA
Wali
David
D
Dennison
Zakia A
ZA
Lamki
Mathew
M
Zachariah
El Banna
el B
Nagwa
Anil
A
Pathare
Rajagopal
R
Krishnamoorthy
D002874:Chromosome Mapping; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000235:genetics*; D009850:Oman; D054353:Perforin / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
D054353:Perforin