Abstract
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive lethal condition characterized by fever, cytopenia, hepatosplenomegaly and hemophagocytosis. The hallmark of FHL is defect apoptosis triggering and lymphocyte cellular cytotoxicity. Thus far three disease-causing genes (PRF1, UNC13D, STX11) have been identified. We performed a genotype-phenotype study in a large, multi-ethnic cohort of 76 FHL patients originating from 65 unrelated families. Biallelic mutations in PRF1, UNC13D and STX11 were demonstrated in 13/74 (18%), 6/61 (10%) and 14/70 (20%) patients, respectively. In 27/60 (45%) patients analyzed for all three genes, no molecular diagnosis was established. STX11 mutations were most common in Turkish families (7/28, 25%), whereas in Middle East families, PRF1 mutations were most frequent (6/13, 46%). No biallelic mutation was identified in most families of Nordic origin (13/14, 93%). Patients carrying PRF1 mutations had higher risk of early onset (age
| Original language | English |
|---|---|
| Pages (from-to) | 75-83 |
| Number of pages | 9 |
| Journal | British Journal of Haematology |
| Volume | 143 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 2008 |
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Keywords
- Familial hemophagocytic lymphohistiocytosis
- Phenotype
- PRF1
- STX11
- UNC13D
ASJC Scopus subject areas
- Hematology
Cite this
Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. / Horne, Annacarin; Ramme, Kim Göransdotter; Rudd, Eva; Zheng, Chengyun; Wali, Yasser; Al-Lamki, Zakia; Gürgey, Aytemiz; Yalman, Nevin; Nordenskjöld, Magnus; Henter, Jan Inge.
In: British Journal of Haematology, Vol. 143, No. 1, 10.2008, p. 75-83.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis
AU - Horne, Annacarin
AU - Ramme, Kim Göransdotter
AU - Rudd, Eva
AU - Zheng, Chengyun
AU - Wali, Yasser
AU - Al-Lamki, Zakia
AU - Gürgey, Aytemiz
AU - Yalman, Nevin
AU - Nordenskjöld, Magnus
AU - Henter, Jan Inge
PY - 2008/10
Y1 - 2008/10
N2 - Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive lethal condition characterized by fever, cytopenia, hepatosplenomegaly and hemophagocytosis. The hallmark of FHL is defect apoptosis triggering and lymphocyte cellular cytotoxicity. Thus far three disease-causing genes (PRF1, UNC13D, STX11) have been identified. We performed a genotype-phenotype study in a large, multi-ethnic cohort of 76 FHL patients originating from 65 unrelated families. Biallelic mutations in PRF1, UNC13D and STX11 were demonstrated in 13/74 (18%), 6/61 (10%) and 14/70 (20%) patients, respectively. In 27/60 (45%) patients analyzed for all three genes, no molecular diagnosis was established. STX11 mutations were most common in Turkish families (7/28, 25%), whereas in Middle East families, PRF1 mutations were most frequent (6/13, 46%). No biallelic mutation was identified in most families of Nordic origin (13/14, 93%). Patients carrying PRF1 mutations had higher risk of early onset (age
AB - Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive lethal condition characterized by fever, cytopenia, hepatosplenomegaly and hemophagocytosis. The hallmark of FHL is defect apoptosis triggering and lymphocyte cellular cytotoxicity. Thus far three disease-causing genes (PRF1, UNC13D, STX11) have been identified. We performed a genotype-phenotype study in a large, multi-ethnic cohort of 76 FHL patients originating from 65 unrelated families. Biallelic mutations in PRF1, UNC13D and STX11 were demonstrated in 13/74 (18%), 6/61 (10%) and 14/70 (20%) patients, respectively. In 27/60 (45%) patients analyzed for all three genes, no molecular diagnosis was established. STX11 mutations were most common in Turkish families (7/28, 25%), whereas in Middle East families, PRF1 mutations were most frequent (6/13, 46%). No biallelic mutation was identified in most families of Nordic origin (13/14, 93%). Patients carrying PRF1 mutations had higher risk of early onset (age
KW - Familial hemophagocytic lymphohistiocytosis
KW - Phenotype
KW - PRF1
KW - STX11
KW - UNC13D
UR - http://www.scopus.com/inward/record.url?scp=51249096022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51249096022&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2008.07315.x
DO - 10.1111/j.1365-2141.2008.07315.x
M3 - Article
C2 - 18710388
AN - SCOPUS:51249096022
VL - 143
SP - 75
EP - 83
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 1
ER -