Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations.
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Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. / Trizzino, A; Zur Stadt, Udo; Ueda, I; Risma, K; Janka, G; Ishii, E; Beutel, Karin; Sumegi, J; Cannella, S; Pende, D; Mian, A; Henter, J-I; Janka-Schaub, Gritta; Santoro, A; Filipovich, A; Aricò, M.
in: J MED GENET, Jahrgang 45, Nr. 1, 1, 2008, S. 15-21.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations.
AU - Trizzino, A
AU - Zur Stadt, Udo
AU - Ueda, I
AU - Risma, K
AU - Janka, G
AU - Ishii, E
AU - Beutel, Karin
AU - Sumegi, J
AU - Cannella, S
AU - Pende, D
AU - Mian, A
AU - Henter, J-I
AU - Janka-Schaub, Gritta
AU - Santoro, A
AU - Filipovich, A
AU - Aricò, M
PY - 2008
Y1 - 2008
N2 - BACKGROUND: PRF1 gene mutations are associated with familial haemophagocytic lymphohistiocytosis type 2 (FHL2). Genotype-phenotype analysis, previously hampered by limited numbers of patients, was for the first time performed by data pooling from five large centres worldwide. PATIENTS AND METHODS: Members of the Histiocyte Society were asked to report cases of FHL2 on specific forms. Data were pooled in a common database and analysed. RESULTS: The 124 patients had 63 different mutations (including 15 novel mutations): 11 nonsense, 10 frameshift, 38 missense and 4 in-frame deletions. Some mutations were found more commonly: 1122 G-->A (W374X), associated with Turkish origin, in 32 patients; 50delT (L17fsX22) associated with African/African American origin, in 21 patients; and 1090-91delCT (L364fsX), in 7 Japanese patients. Flow cytometry showed that perforin expression was absent in 40, reduced in 6 and normal in 4 patients. Patients presented at a median age of 3 months (quartiles: 2, 3 and 13 months), always with fever, splenomegaly and thrombocytopenia. NK activity was absent in 36 (51%), 5% in 4 (6%), "reduced" in 2 (3%) (not reported, n = 54). Nonsense mutations were significantly associated with younger age at onset (p
AB - BACKGROUND: PRF1 gene mutations are associated with familial haemophagocytic lymphohistiocytosis type 2 (FHL2). Genotype-phenotype analysis, previously hampered by limited numbers of patients, was for the first time performed by data pooling from five large centres worldwide. PATIENTS AND METHODS: Members of the Histiocyte Society were asked to report cases of FHL2 on specific forms. Data were pooled in a common database and analysed. RESULTS: The 124 patients had 63 different mutations (including 15 novel mutations): 11 nonsense, 10 frameshift, 38 missense and 4 in-frame deletions. Some mutations were found more commonly: 1122 G-->A (W374X), associated with Turkish origin, in 32 patients; 50delT (L17fsX22) associated with African/African American origin, in 21 patients; and 1090-91delCT (L364fsX), in 7 Japanese patients. Flow cytometry showed that perforin expression was absent in 40, reduced in 6 and normal in 4 patients. Patients presented at a median age of 3 months (quartiles: 2, 3 and 13 months), always with fever, splenomegaly and thrombocytopenia. NK activity was absent in 36 (51%), 5% in 4 (6%), "reduced" in 2 (3%) (not reported, n = 54). Nonsense mutations were significantly associated with younger age at onset (p
M3 - SCORING: Zeitschriftenaufsatz
VL - 45
SP - 15
EP - 21
JO - J MED GENET
JF - J MED GENET
SN - 0022-2593
IS - 1
M1 - 1
ER -
