Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Blood. 2011 Jul 21;118(3):493-8. doi: 10.1182/blood-2011-03-341560. Epub 2011 May 11.
A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition.
家族性霍奇金淋巴瘤在某些家族中存在明显聚集现象早已得到公认。然而，家族性霍奇金淋巴瘤的遗传背景中的基因因素在很大程度上仍是未知的。我们研究了一个有 4 个表亲的家族，他们患有罕见亚型的疾病，结节性淋巴细胞为主型霍奇金淋巴瘤。我们对这个家族应用外显子组测序和全基因组连锁分析，发现了核蛋白共济失调毛细血管扩张症突变易感基因（NPAT）基因中的一个截断性种系突变，该突变在家族中发生了遗传。我们还研究了大量来自其他霍奇金淋巴瘤患者的样本，发现了导致丝氨酸 724 缺失的种系变异，这表明该疾病的风险增加（比值比=4.11；P=.018）。到目前为止，NPAT 是第一个被认为与结节性淋巴细胞为主型霍奇金淋巴瘤易感性相关的基因。
