Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation

Susan Molleran Lee, Janos Sumegi, Joyce Villanueva, Yasuhiro Tabata, Kejian Zhang, Ranajit Chakraborty, Xiaohua Sheng, Rita Clementi, Genevieve de Saint Basile, Alexandra H. Filipovich

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Abstract

Mutations of the perforin gene (PRF1) are present in a proportion of patients with hemophagocytic lymphohistiocytosis (HLH). We found that all identified infants with HLH of African descent (17 from USA, 4 from Europe) have 50delT-PRF1 (16 homozygotes, 5 compound heterozygotes), accounting for the most frequently observed PRF1 mutation. Two additional patients with HLH, self-reporting as Hispanic, carried 50delT, but no Caucasians were identified with 50delT. To test the hypothesis that this mutation represents a single haplotype, DNA from 23 patients with HLH and 30 African-American control subjects was sequenced for the PRF1 gene, including portions of the intron containing known single nucleotide polymorphisms (SNPs). The same groups were genotyped at 3 microsatellites proximal to PRF1. The SNP profiles of patients with 50delT-PRF1 were identical, and 5 novel SNPs were identified among African-American control subjects. Patients with 50delT-PRF1 were also found to have had an earlier age of disease onset than patients with other PRF1 mutations. Extent of haplotype sharing and variability of microsatellite alleles in 50delT-PRF1 chromosomes suggest that this mutation arose approximately 1000 to 4000 years ago and is restricted to patients of African descent.

Original languageEnglish (US)
Pages (from-to)134-137
Number of pages4
JournalJournal of Pediatrics
Volume149
Issue number1
DOIs
Publication statusPublished - Jul 1 2006

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Lee, S. M., Sumegi, J., Villanueva, J., Tabata, Y., Zhang, K., Chakraborty, R., ... Filipovich, A. H. (2006). Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. Journal of Pediatrics, 149(1), 134-137. https://doi.org/10.1016/j.jpeds.2006.03.003