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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
Pages (from-to)134-137
Number of pages4
JournalJournal of Pediatrics
Volume149
Issue number1
DOIs
StatePublished - 1 Jul 2006

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Hemophagocytic Lymphohistiocytosis
Haplotypes
Mutation
Single Nucleotide Polymorphism
African Americans
Microsatellite Repeats
Perforin
Homozygote
Heterozygote
Age of Onset
Hispanic Americans
Introns
Genes
Chromosomes
Alleles
DNA

Cite this

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
Lee, Susan Molleran ; Sumegi, Janos ; Villanueva, Joyce ; Tabata, Yasuhiro ; Zhang, Kejian ; Chakraborty, Ranajit ; Sheng, Xiaohua ; Clementi, Rita ; de Saint Basile, Genevieve ; Filipovich, Alexandra H. / Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. In: Journal of Pediatrics. 2006 ; Vol. 149, No. 1. pp. 134-137.
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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.",
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Lee, SM, Sumegi, J, Villanueva, J, Tabata, Y, Zhang, K, Chakraborty, R, Sheng, X, Clementi, R, de Saint Basile, G & Filipovich, AH 2006, 'Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation', Journal of Pediatrics, vol. 149, no. 1, pp. 134-137. https://doi.org/10.1016/j.jpeds.2006.03.003

Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. / Lee, Susan Molleran; Sumegi, Janos; Villanueva, Joyce; Tabata, Yasuhiro; Zhang, Kejian; Chakraborty, Ranajit; Sheng, Xiaohua; Clementi, Rita; de Saint Basile, Genevieve; Filipovich, Alexandra H.

In: Journal of Pediatrics, Vol. 149, No. 1, 01.07.2006, p. 134-137.

Research output: Contribution to journalArticle

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T1 - Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation

AU - Lee, Susan Molleran

AU - Sumegi, Janos

AU - Villanueva, Joyce

AU - Tabata, Yasuhiro

AU - Zhang, Kejian

AU - Chakraborty, Ranajit

AU - Sheng, Xiaohua

AU - Clementi, Rita

AU - de Saint Basile, Genevieve

AU - Filipovich, Alexandra H.

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N2 - 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.

AB - 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.

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