Cheryl Weiqi Tan, Gayatiri Raveentheran, Khadijah Rafi'ee, Lena Das, Mark Jean-Aan Koh, Ene-Choo Tan
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引用次数: 0
Abstract
Background: Kikuchi-Fujimoto disease (KFD) is a rare disorder involving necrotizing lymphadenitis which was first described in Japan. The presentations include lymphadenopathy, fever, and leukopenia of unknown cause.
Patient: A 2-year-old Malay girl was evaluated and diagnosed with KFD after presenting with prolonged fever and rash. Her parents are not biologically related, but there is a strong family history of KFD on the maternal side of the family. We investigated the genetic profiles of the patient, her mother and grandmother, who also had a history of similar presentations.
Methods: High-resolution HLA typing was performed on the family to examine the potential associations with HLA genotypes. Next-generation sequencing using a Mendelian gene panel was performed on the child's sample, followed by targeted Sanger sequencing of shortlisted variants for the family members.
Results: The three affected family members share 14 HLA alleles that are not present in the healthy father, among which five have reported associations with autoimmune inflammatory disorders. Two of them (DQA1*02:01 and DRB1*07:01) were also reported in a pair of affected twins from Australia. In addition to HLA, three rare missense variants in immune-related genes (FGFR3, NRP2 and PCM1) were found to correlate with the presence of symptoms within the family. The three affected members also had at least one of the variants in the C1QC gene (a missense and a 17-nucleotide deletion), which is part of the complement pathway that might be related to KFD.
Conclusion: Our study uncovers some HLA alleles and immune gene variants that might be important in the development of KFD. Large-scale sequencing of immune genes may be as important as high-resolution HLA typing in identifying genetic factors contributing to KFD pathogenesis. HLA studies provide risk associations to KFD, while association with variants in immune genes may reveal pathways in the development of KFD.
期刊介绍：
Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability.
In particular, emphasis will be given to:
Genomic and proteomic profiling
Genetics and drug metabolism
Targeted drug identification and discovery
Optimizing drug selection & dosage based on patient''s genetic profile
Drug related morbidity & mortality intervention
Advanced disease screening and targeted therapeutic intervention
Genetic based vaccine development
Patient satisfaction and preference
Health economic evaluations
Practical and organizational issues in the development and implementation of personalized medicine programs.
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