title: [Analysis of clinical phenotype and genetic mutations of a pedigree of familial hemophagocytic lymphohistiocytosis].
abstract: OBJECTIVE
  To analyze mutations in a pedigree of familial hemophagocytic lymphohistiocytosis (FHLH) from Sichuan and provide genetic counseling for the family.
  
  
  METHODS
  Clinical data of a case with FHLH diagnosed at West China Second Hospital was retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Eight candidate genes for primary HLH were amplified with PCR and analyzed by direct sequencing.
  
  
  RESULTS
  The proband was diagnosed as HLH based on clinical manifestations of recurrent fever for 2 months, hepatosplenomegaly, lymphadenopathy, pancytopenia, hyperferritinemia, and decreased fibrinogen and hemophagocytosis in bone marrow. Genetic testing for primary HLH was carried out considering the relapse of illness after hormone therapy for 8 weeks and the family history. The results of gene sequencing showed that the proband has carried compound heterozygous mutations in PRF1 gene (c.1349C> T in exon 3 and c.445G> A in exon 2). His father has carried a heterozygous mutation (c.445G> A in exon 2) and nonsense mutation (c.900C> T in exon 3), and his mother carried a heterozygous mutation (c.1349C> T in exon 3). Both c.1349C> T and c.445G> A have been previously reported as pathogenic mutations.
  
  
  CONCLUSIONS
  The family has been diagnosed as familial HLH type 2 based on clinical and laboratory examinations and molecular genetic testing. Gene sequencing has indicated that is was a recessive type familial HLH.
authors.affiliation: Department of Pediatric Hematology and Oncology; Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R.China. guoxkl@163.com.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Sun
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D054353:Perforin / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: C510468:PRF1 protein, human; D054353:Perforin