Mhatre Snehal, Madkaikar Manisha, Desai Mukesh, Ghosh Kanjaksha
National Institute of Immunohaematology, 13th floor KEM Hospital, Parel, Mumbai 400012, India.
National Institute of Immunohaematology, 13th floor KEM Hospital, Parel, Mumbai 400012, India.
Blood Cells Mol Dis. 2015 Mar;54(3):250-7. doi: 10.1016/j.bcmd.2014.11.023. Epub 2014 Dec 23.
Inherited perforin deficiency is a rare autosomal recessive disorder that causes severe form of hemophagocytic lymphohistiocytosis (FHL2). The main aim of this study was to analyze the nature of gene mutations in a cohort of Indian patients with FHL2 and to utilize this knowledge for genetic counseling and prenatal diagnosis.
13 HLH patients with abnormal perforin expression on NK cells by flow cytometry were included in the study. The entire coding region and intronic splice sites of the PRF1 gene were sequenced from the genomic DNA of these patients.
10 patients from the present series had an early presentation with severe clinical manifestations, while 3 had a delayed onset with unusual presenting features viz Hodgkin's lymphoma, tuberculosis and acute lymphoblastic leukemia. Sequence analysis revealed 11 different mutations (8 novel and 3 previously reported) spread over the entire coding region of PRF1 gene. Missense mutation Trp129Ser in heterozygous state was present in all the 3 patients with a delayed onset of the disease.
A wide heterogeneity was observed in the nature of mutations in Indian FHL2 patients. Molecular characterization of PRF1 gene was not only used in the confirmation of diagnosis but also in genetic counseling and pre-natal diagnosis in affected families.
遗传性穿孔素缺乏症是一种罕见的常染色体隐性疾病，可导致严重形式的噬血细胞性淋巴组织细胞增生症（FHL2）。本研究的主要目的是分析一组印度FHL2患者的基因突变性质，并将这一知识用于遗传咨询和产前诊断。
本研究纳入了13例通过流式细胞术检测发现自然杀伤细胞上穿孔素表达异常的HLH患者。从这些患者的基因组DNA中对PRF1基因的整个编码区和内含子剪接位点进行测序。
本系列中的10例患者早期出现严重临床表现，而3例发病延迟，具有不寻常的表现特征，即霍奇金淋巴瘤、结核病和急性淋巴细胞白血病。序列分析揭示了11种不同的突变（8种新突变和3种先前报道的突变），分布在PRF1基因的整个编码区。所有3例发病延迟的患者均存在杂合状态的错义突变Trp129Ser。
在印度FHL2患者中观察到突变性质存在广泛的异质性。PRF1基因的分子特征不仅用于确诊，还用于受影响家庭的遗传咨询和产前诊断。
