Three Consecutive Cases of Familial Hemophagocytic Lymphohistiocytosis, Including a Case Due to Maternal Uniparental Disomy

J Pediatr Hematol Oncol. 2020 Nov;42(8):e819-e821. doi: 10.1097/MPH.0000000000001681.


We have experienced 3 consecutive cases of familial hemophagocytic lymphohistiocytosis (FHL). All affected infants had mutations in exon 3 of the perforin gene. The first had a homozygous mutation, c.1168C>T (p.R390*), caused by maternal uniparental isodisomy. The second and third had compound heterozygous mutations: c.781G>A (p.E261K) and c.1491T>A (p.C497*); c.1724G>T (p.C242G) and p.R390*, respectively. FHL is very rare in Northern Japan but should be suspected if infants exhibit prolonged fever. This is the first report of a relationship of p.R390* with FHL caused by uniparental isodisomy, and the second reported case of FHL type 2 with this form of inheritance.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphohistiocytosis, Hemophagocytic / etiology
  • Lymphohistiocytosis, Hemophagocytic / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Perforin / genetics*
  • Prognosis
  • Uniparental Disomy / genetics
  • Uniparental Disomy / pathology*


  • PRF1 protein, human
  • Perforin

Supplementary concepts

  • Hemophagocytic lymphohistiocytosis, familial, 2