Familial hemophagocytic lymphohistiocytosis type 2 in a female Chinese neonate: A case report and review of the literature

Figure 1 Gene sequencing results of the index case and some family members. A: Sanger sequencing revealed that the child had a compound heterozygous mutation of PRF1 gene consisting of c.658G>C (p.Gly220Arg) and c.1066C>T (p.Arg356Trp); B: The paternal grandfather and father were heterozygous for c.658G>C (p.Gly220Arg) while the maternal grandmother and mother were heterozygous for c.1066C>T (p.Arg356Trp). The healthy sister did not carry any perforin-1 (PRF1) gene mutation. The eldest brother died at the age of 3 mo, more than 13 years ago, with recurrent fever and jaundice without diagnosis. C: Protein alignment shows that both Gly220 and Arg356 are highly conserved among many animal species; D: Gly220Arg mutation causes molecular collision between Arg220, Arg55, and Ser56 (the pink dotted line in the white box), and Arg356Trp mutation causes hydrogen bond breaks between Trp356, Leu197, Asp354, and Pro355 (green dashed line in the orange box). Both mutations change the conformation of PRF1 protein and decrease the protein function.