Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis

Annacarin Horne, Kim Göransdotter Ramme, Eva Rudd, Chengyun Zheng, Yasser Wali, Zakia Al-Lamki, Aytemiz Gürgey, Nevin Yalman, Magnus Nordenskjöld, Jan Inge Henter

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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 languageEnglish
Pages (from-to)75-83
Number of pages9
JournalBritish Journal of Haematology
Volume143
Issue number1
DOIs
Publication statusPublished - Oct 2008

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Keywords

  • Familial hemophagocytic lymphohistiocytosis
  • Phenotype
  • PRF1
  • STX11
  • UNC13D

ASJC Scopus subject areas

  • Hematology

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