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Objective: X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. XLP patient displays EBV associated fulminant infectious mononucleosis or hemophagocytic lymphohistocytosis, hypogammaglobulinemia or malignant lymphoma. Here we report the clinical features, gene mutation and SAP expression on PBMCs of a Chinese patient with XLP and potential carriers., Method: A 6 years old male patient and his maternal relatives were enrolled in this study. The patient was found to have with a renal Burkitt lymphoma on the right waist at 5 years of age by accident. His elder brother and a maternally related cousin both died of multiple systemic organ dysfunction syndrome (MODS) due to fulminant infectious mononucleosis (FIM) at the age of one year. The patient and his maternal relatives were subjected to detection of SAP expression on the PBMCs by flow cytometry and gene mutation analysis of SH2D1A by using PCR based on genomic DNA., Result: The patient exhibited 536.9 copy/ml level of circulating EBV-DNA during remission. Sequence analysis showed that the patient harbored a nonsense mutation in exon 2 (C462T), resulting in a premature stop codon (Arg55X). His mother and some of the maternal relatives were proved to be carriers of this mutation. SAP expression from the patient was significantly reduced as compared to normal individual and the carriers., Conclusion: We identified a Chinese XLP case genetically. Assessment of SAP expression on PBMCs by flow cytometry seemed to be an effective rapid diagnostic method for this disease. Absence of EBV infection does not diminish the possibility of XLP.

Objective: To verify the pathogenesis in Chinese and to investigate the genetic rule of X-linked lymphoproliferative disease (XLP) therein., Methods: The case history of a proband of XLP, male, aged 1 year and 5 months, who died 40 days after hospitalization, was reviewed. Fourteen his family members were interviewed for the development history, anamnesis, and underwent physical examination. Single-strand conformation polymorphism (SSCP-PCR) and sequencing were used to detect the SH2D1A mutation among the elder sister, younger brother, and parents of the poband., Results: The proband and his elder brother suffered with virus-associated hemophagocytic syndrome and both died in 40 days after the disease coming on in the last two years in succession. The second exon of SH2D1A of the younger brother of the proband showed a nonsense mutation in SH2D1A gene: the C-T nucleotide substitution at nucleotide position 462 result in a stop codon and pre-mature termination of protein synthesis. The mother was proved as mutation heterozygote of the C and T nucleotide on the same site. The other members of the family were proved normal. The clinical manifestation of the younger brother of the proband was Langerhans cell histiocytosis., Conclusion: Langerhans cell histiocytosis may be a new clinical phenotype of XLP. The gene of SH2D1A is responsible for the disease of XLP in Chinese too. The newly developed method of SH2D1A mutation analysis may be suitable in the diagnosis of XLP in Chinese.