【摘 要】
：
肺泡微结石症(pulmonary alveolar microlithiasis,PAM)是一种罕见的肺部疾病,以磷酸钙盐颗粒在肺泡内沉积为特征,有家族遗传倾向,多以常染色体隐性方式遗传.PAM患者早期症状不明显,可在30-40岁之间逐渐出现干咳、呼吸困难、咯血、气胸及肺心病等症状.临床上主要通过X线或胸部CT对PAM进行确诊,患者双肺可见弥漫性砂粒样钙化结节影,且随病情进展钙化灶逐渐增多并出现聚
【机 构】
：
华中科技大学分子生物物理教育部重点实验室和生命科学与技术学院,武汉,430074 南阳市中心医院呼
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肺泡微结石症(pulmonary alveolar microlithiasis,PAM)是一种罕见的肺部疾病,以磷酸钙盐颗粒在肺泡内沉积为特征,有家族遗传倾向,多以常染色体隐性方式遗传.PAM患者早期症状不明显,可在30-40岁之间逐渐出现干咳、呼吸困难、咯血、气胸及肺心病等症状.临床上主要通过X线或胸部CT对PAM进行确诊,患者双肺可见弥漫性砂粒样钙化结节影,且随病情进展钙化灶逐渐增多并出现聚集融合,呈现"雪暴样"改变.研究发现SLC34A2基因突变是导致PAM的原因,该基因编码Ⅱ型钠磷转运体NaPi-Ⅱb.在肺部,SLC34A2只在Ⅱ型肺泡上皮细胞中表达,这种细胞负责合成并分泌肺泡表面活性物质(Pulmonary surfactant,PS).目前认为NaPi-Ⅱb的主要作用是从肺泡液中吸收无机磷用于PS的合成,其转运活性的丧失导致肺泡内无积磷积累,进而引发磷酸钙盐的沉积.本研究收集了一个中国肺泡微结石症家系,先证者胸部CT显示肺泡微石结晶并伴随肺纤维化,血清钙、磷水平正常；其父亲胸部CT检查也发现肺泡微晶石,但程度较轻,未表现出临床症状；先证者的1个妹妹和1弟弟均患PAM疾病已经死亡,而姑姑曾患肺结核.直接对SLC34A2基因测序,发现先证者携带一对杂合突变(c.394C ＞T/p.Q 132*和c.569T＞A/p.I190N),其父亲及姑姑均携带c.569T＞A/p.I190N突变,母亲携带c.394C ＞T/p.Q132*突变.c.394C＞T突变为无义突变,推测异常mRNA很可能通过NMD途径降解；c.569T＞A突变位于NaPi-Ⅱb蛋白N端的钠磷共转运结构域,导致第190位高度保守的异亮氨酸变为天冬氨酸,推测可能会影响NaPi-Ⅱb的无机磷转运活性.目前报道的家族性肺泡微石症患者大多为同胞兄弟姊妹,其父母及子女极少发病.本研究收集的家系中,先证者及其父亲均有肺泡钙化现象,但先证者发病较早,临床表型也更为严重,说明携带双突变的患者病情进展较携带单突变的患者快.综上所述,本研究收集了一个两代连续遗传的肺泡微石症家系,并鉴定出SLC34A2基因一个复合型杂合新突变,基因型表型分析发现携带SLC34A2双突变(c.394C＞T和c.569T＞A)的患者临床表型较携带单突变(c.569T＞A)的患者严重.
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