家族性特发性肺间质纤维化家系的临床特征及遗传学特点

Abstract

目的 通过观察家族性特发性肺间质纤维化(FIPF)的临床特点并检测相关基因,明确特发性肺间质纤维化(IPF)表现形式,了解相关发病机制,寻找可能的治疗方法.方法 收集1970-2014年确诊的1个中国北方汉族FIPF家系连续3代共7例患者,其中男4例,女3例,发病年龄30～57岁.先证者为Ⅱ-4,最先发病者为Ⅰ-1,Ⅱ代6名成员中5例发病,其中男2例,女3例,Ⅲ代11名成员中目前l例成年男性发病,遗传特点符合常染色体显性遗传.通过影像学及肺功能等检查确诊IPF.搜集家族成员基本信息、影像学及病理学检查等临床资料,分析病情特点并比较临床表现,并进行肺组织病理学检查以及基因检测.结果 该家系发病后平均生存期3年,糖皮质激素(激素)治疗效果欠佳.3例临床资料完整的患者间质性肺疾病相关免疫学检查结果均为阴性.3例肺功能可见明显限制性通气功能障碍,DLCO分别为50％、23％和46％,弥散功能严重减低.3例影像学资料完整的患者,1例表现为UIP,2例表现为NSIP.3例影像学表现虽然不同,但应用激素治疗均效果不佳,其中2例死亡.对该家系中Ⅱ-4患者进行了外周血基因检测和尸检.结论 家族性肺间质纤维化家族患病成员平均死亡年龄为50.2岁,患者影像学特征和病理表现可表现为UIP或NSIP,即使肺活检病理诊断为NSIP,激素治疗也可能无效.该家系中Ⅱ-4患者基因检测未检出TERT、TERC和SFPTC基因突变.

Objective To identify the manifestations and pathogenesis of idiopathic pulmonary fibrosis (IPF) after studying the clinical features of familial idiopathic pulmonary fibrosis (FIPF) and detecting relevant genes.Methods Seven persons with FIPF from one family of Han nationality in northern China,which had FIPF patients in three consecutive generations,were included in this study.The incidence age of the 7 subjects (4 males and 3 females) ranged from 30 to 57 years.The propositus was Ⅱ-4,while the first person attacked by FIPF was Ⅰ-1.Five patients (2 males,3 females) in the second generation and one case in the third generation were found at the time of this study.The genetic characteristics of FIPF in this study were complied with the pattern of autosomal dominant inheritance.Imaging examinations and pulmonary function tests were conducted to confirm the diagnosis of pulmonary fibrosis.Meanwhile,personal information and clinical data such as imaging examinations and pathological tests were acquired;clinical features and manifestations were analyzed and compared;and pathological tests and gene detection were performed.Results The average survival time was 3 years,and poor response to glucocorticoid treatment was observed.Three patients had detailed clinical information,whose interstitial pneumonia related immunologic tests were negative.Concerning pulmonary function,three patients had significant decrease of diffusion function and obvious restrictive ventilatory disorder,with DLCO value as 50％,23％ and 46％,respectively.Among the 3 patients with complete imaging data,1 was considered as UIP,while 2 as NSIP.The 3 subjects who had different imaging findings all responded poorly to glucocorticoid treatment,and two of them died.Genetic test for TERT,TERC and SFTPC in peripheral blood and autopsy were performed for Ⅱ-4 but all were negative.Conclusions The average death age of family members with FIPF was 50.2 years.The patients presented various imaging features and pathological findings.Glucocorticoid treatment may be ineffective,even for persons diagnosed as NSIP by lung biopsy.