Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency
Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency
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DOI：
10.1164/ajrccm.161.3.9903153
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发表时间：
2000-03-01
影响因子：
24.7
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Nogee, LM;Wert, SE;Whitsett, JA
不能产生表面活性蛋白B（SP-B）导致致命的新生儿呼吸道疾病。移码突变（121 ins 2）是主要的，但不是唯一的疾病原因。为了确定SP-B缺乏症的机制范围，对32名受影响婴儿的两个等位基因进行了表征。16名婴儿为121 ins 2突变纯合子，10名婴儿为121 ins 2和另一种突变杂合子，6名婴儿为其他突变纯合子。13个新的SP-B基因突变被确定，这是没有发现在对照人群。在两个不相关的家族中发现了一个新的突变。通过免疫组织化学和/或蛋白质印迹法评价表面活性剂蛋白表达。proSP-B和成熟SP-B的缺失与无义突变和移码突变相关。相比之下，proSP-B表达与错义突变或导致框内缺失或插入的突变相关，低水平的成熟SP-B表达与四种突变相关。在所有SP-B基因突变婴儿的肺中观察到proSP-C和/或异常处理的SP-C的细胞外染色。遗传性SP-B缺乏症是由SP-R基因中的各种不同突变引起的，并且可能与成熟SP-B水平降低以及缺乏相关，这可能是由proSP-B加工受损引起的。
Inability to produce surfactant protein B (SP-B) causes fatal neonatal respiratory disease. A frameshift mutation (121ins2) is the predominant but not exclusive cause of disease. To determine the range of mechanisms responsible for SP-B deficiency, both alleles from 32 affected infants were characterized. Sixteen infants were homozygous for the 121ins2 mutation, 10 infants were heterozygous for the 121ins2 and another mutation, and six infants were homozygous for other mutations. Thirteen novel SP-B gene mutations were identified, which were not found in a control population. One novel mutation was found in two unrelated families. Surfactant protein expression was evaluated by immunohistochemistry and/or protein blotting. Absence of proSP-B and mature SP-B was associated with nonsense and frame-shift mutations. In contrast, proSP-B expresssion was associated with missense mutations, or mutations causing in-frame deletions or insertions, and low levels of mature SP-B expression were associated with four mutations. Extracellular staining for proSP-C and/or aberrantly processed SP-C was observed in lungs of all infants with SP-B gene mutations. Hereditary SP-B deficiency is caused by a variety of distinct mutations in the SP-R gene and may be associated with reduced, as well as absent, levels of mature SP-B, likely caused by impaired processing of proSP-B.