TY - JOUR
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.
PY - 2006/7
Y1 - 2006/7
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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U2 - 10.1016/j.jpeds.2006.03.003
DO - 10.1016/j.jpeds.2006.03.003
M3 - Article
C2 - 16860143
AN - SCOPUS:33746138137
VL - 149
SP - 134
EP - 137
JO - Journal of Pediatrics
JF - Journal of Pediatrics
SN - 0022-3476
IS - 1
ER -