Ballard P L, Nogee L M, Beers M F, Ballard R A, Planer B C, Polk L, deMello D E, Moxley M A, Longmore W J
Department of Pediatrics, University of Pennsylvania, Children's Hospital of Philadelphia 19104, USA.
Pediatrics. 1995 Dec;96(6):1046-52.
To evaluate components of pulmonary surfactant and identify mutations in the surfactant protein B gene (SP-B) of a term infant with severe respiratory distress and chronic lung disease. PATIENT AND TESTING: Respiratory distress developed in an infant delivered at term, and he required extracorporeal bypass support for 2 weeks. Until his unexpected death at 9.5 months, he was ventilator and oxygen dependent and required continual dexamethasone therapy. Tracheobronchial lavage samples were analyzed for content of surfactant proteins (SPs), and DNA from blood samples were sequenced and analyzed by polymerase chain reaction restriction analysis for the presence of SP-B gene mutations. Surfactant lipid composition and function, the contents of SPs and their messenger RNAs (mRNAs), and the immunostaining pattern for SPs were determined in postmortem lung tissue.
The lavage sample contained SP-A but not SP-B, and DNA restriction analysis indicated that the patient and his mother were heterozygous for the previously described 121ins2 mutation of SP-B. Postmortem lung tissue contained normal levels of SP-A and its mRNA, a low but detectable level of SP-B, and near normal content of SP-B mRNA. SP-C was abundant on staining, and some 6-kd precursor was present in tissue. A surfactant fraction was deficient in phosphatidylglycerol and was not surface active. On DNA sequencing, a point mutation was found in exon 7 of the patient's SP-B gene allele without the 121ins2 mutation, resulting in a cysteine for arginine substitution, and the father was a carrier for the same mutation.
We describe a patient who is a compound heterozygote with a new mutation and only a partial deficiency of SP-B. Some forms of inherited SP-B deficiency may have low expression of immunoreactive and possibly functional SP-B with milder lung disease and longer survival. These infants may benefit from glucocorticoid therapy and may not develop antibodies to SP-B after either lung transplant or gene therapy.
评估肺表面活性物质的成分，并鉴定一名患有严重呼吸窘迫和慢性肺病的足月儿的表面活性蛋白B基因（SP-B）突变情况。
一名足月儿出生后出现呼吸窘迫，需要体外循环支持2周。在其9.5个月意外死亡前，一直依赖呼吸机和氧气，并需要持续的地塞米松治疗。对气管支气管灌洗样本进行表面活性蛋白（SPs）含量分析，对血样DNA进行测序，并通过聚合酶链反应限制性分析检测SP-B基因突变情况。测定死后肺组织中的表面活性物质脂质成分和功能、SPs及其信使核糖核酸（mRNAs）的含量，以及SPs的免疫染色模式。
灌洗样本中含有SP-A但不含SP-B，DNA限制性分析表明，该患者及其母亲对于先前描述的SP-B 121ins2突变是杂合子。死后肺组织中SP-A及其mRNA水平正常，SP-B水平低但可检测到，SP-B mRNA含量接近正常。SP-C染色丰富，组织中存在一些6-kD前体。一种表面活性物质组分中磷脂酰甘油缺乏，且无表面活性。DNA测序发现，患者未发生121ins2突变的SP-B基因等位基因第7外显子存在一个点突变，导致半胱氨酸替代精氨酸，父亲是同一突变的携带者。
我们描述了一名患有新突变且仅存在部分SP-B缺乏的复合杂合子患者。某些形式的遗传性SP-B缺乏可能具有免疫反应性和可能功能性SP-B的低表达，伴有较轻的肺病和较长的生存期。这些婴儿可能从糖皮质激素治疗中获益，并且在肺移植或基因治疗后可能不会产生针对SP-B的抗体。
