摘要
目的对1个四川籍家族性噬血细胞综合征（familial hemophagocytic lymphohistiocytosis，FHLH）家系进行基因突变分析，为其家系成员提供准确的病因诊断和遗传咨询。方法分析1例FHLH先证者的临床病例资料，应用聚合酶链反应对先证者及父母与原发性噬血细胞综合征（primary hemophagocytic lymphohistiocytosis，pHLH）发病相关的8个致病基因（PRF1、Unc13D、STX11、STXBP2、RAB27A、LYST、SH2D1A、B侬C4）进行扩增，对扩增产物进行测序和序列分析。结果先证者临床表现为反复发热2’月，肝脾淋巴结肿大，外周血三系降低，高铁蛋白血症，低纤维蛋白原血症，骨髓检查见组织细胞吞噬血细胞，噬血细胞综合征诊断明确，使用激素治疗8周停药后病情反复，先证者有可疑家族史。测序结果显示先证者PRF1基因第3外显子存在c．1349C〉T（P．Thr450Met）杂合错义突变和第2外显子c．445G〉A（P．Gly149Ser）杂合错义突变；先证者父亲PRF1基因第2外显子存在C．445G〉A杂合错义突变（P．Gly149Ser）和第3外显子C．900C〉T同义突变（P．His300His）；先证者母亲PRn基因第3外显子存在C．1349C〉T杂合错义突变（P．Thr450Met）。PRF1基因第3外显子C．1349C〉T（P．Thr450Met）和第2外显子c．445G〉A（P．Gly149Ser）突变均为已报道的致病性突变。结论根据先证者临床表现、实验室检查及家系分子遗传学检测结果，可临床诊断为FHLH-2型患者。基因测序结果表明这是一个常染色体隐性遗传的家族性噬血细胞综合征家系。
] Objective To analyze mutations in a pedigree of familial hemophagocytic lymphohistioeytosis （FHLH） from Siehuan and provide genetic counseling for the family. Methods Clinical data of a case with FHLH diagnosed at West China Second Hospital was retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Eight candidate genes for primary HLH were amplified with PCR and analyzed by direct sequencing. Results The proband was diagnosed as HLH based on clinical manifestations of recurrent fever for 2 months, hepatosplenomegaly, lymphadenopathy, pancytopenia, hyperferritinemia, and decreased fibrinogen and hemophagocytosis in bone marrow. Genetic testing for primary HLH was carried out considering the relapse of illness after hormone therapy for 8 weeks and the family history. The results of gene sequencing showed that the proband has carried compound heterozygous mutations in PRFI gene （c. 1349C〉T in exon 3 and c. 445G〉A in exon 2）. His father has carried a heterozygous mutation （c. 445G〉A in exon 2） and nonsense mutation （c. 900C：〉T in exon 3）, and his mother carried a heterozygous mutation （c. 1349C〉T in exon 3）. Both co 1349C〉T and c. 445G〉A have been previously reported as pathogenic mutations. Conclusion The family has been diagnosed as familial HLH type 2 based on clinical and laboratory examinations and molecular genetic testing. Gene sequencing has indicated that is was a recessive type familial HLH.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2014年第5期570-573,共4页
Chinese Journal of Medical Genetics
基金
教育部博士点基金一新教师类（20120181120050）
关键词
家族性噬血细胞综合征
PRF1基因
复杂性杂合突变
Familial hemophagocytic lymph-ohistiocytosis
PRF1 gene
Con：pound heterozygous mutation
