表面活性蛋白C相关性间质性肺疾病；同一SFTPC突变的三种不同表型
Surfactant Protein C-associated interstitial lung disease; three different phenotypes of the same SFTPC mutation.
作者信息
Salerno Teresa, Peca Donatella, Menchini Laura, Schiavino Alessandra, Boldrini Renata, Esposito Fulvio, Danhaive Olivier, Cutrera Renato
机构信息
Pneumology Unit - Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Piazza S Onofrio 4, 00165, Rome, Italy.
Research Laboratory, Bambino Gesù Children's Hospital, IRCCS, Piazza S Onofrio 4, 00165, Rome, Italy.
出版信息
Ital J Pediatr. 2016 Feb 29;42:23. doi: 10.1186/s13052-016-0235-x.
Abstract
BACKGROUND
Monoallelic mutations of the Surfactant Protein C gene (SFTPC) are associated with Interstitial Lung Disease in children. I73T is the most common mutation, accounting for 30 % of all cases reported.
CASE PRESENTATION
We describe three patients carrying the same I73T SPC mutation with very different phenotypes, clinical course (ranging from mild respiratory symptoms to death for respiratory failure) and outcome.
CONCLUSIONS
The disease mechanisms associated with SP-C mutations suggest that the combination of individual genetic background and environmental factors contribute largely to the wide variability of clinical expression. Infants, children and adults with ILD of unknown etiology should be investigated for SP-C genetic abnormalities.
摘要
背景
表面活性蛋白C基因（SFTPC）的单等位基因突变与儿童间质性肺疾病相关。I73T是最常见的突变，占所有报道病例的30%。
病例报告
我们描述了三名携带相同I73T SPC突变的患者，其具有非常不同的表型、临床病程（从轻度呼吸道症状到因呼吸衰竭死亡）和结局。
结论
与SP-C突变相关的疾病机制表明，个体遗传背景和环境因素的组合在很大程度上导致了临床表型的广泛变异性。病因不明的ILD婴儿、儿童和成人应进行SP-C基因异常的调查。
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本文引用的文献
1
European protocols for the diagnosis and initial treatment of interstitial lung disease in children.欧洲儿童间质性肺疾病诊断和初始治疗方案。
Thorax. 2015 Nov;70(11):1078-84. doi: 10.1136/thoraxjnl-2015-207349. Epub 2015 Jul 1.
2
Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations.与表面活性蛋白C突变相关的弥漫性肺疾病的临床和超微结构谱
Eur J Hum Genet. 2015 Aug;23(8):1033-41. doi: 10.1038/ejhg.2015.45. Epub 2015 Mar 18.
3
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Am J Physiol Lung Cell Mol Physiol. 2015 Jan 1;308(1):L33-47. doi: 10.1152/ajplung.00217.2014. Epub 2014 Oct 24.
4
An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy.美国胸科学会官方临床实践指南：婴幼儿特发性间质性肺疾病的分类、评估和管理。
Am J Respir Crit Care Med. 2013 Aug 1;188(3):376-94. doi: 10.1164/rccm.201305-0923ST.
5
Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury.基因替换表面活性蛋白-C 可减轻呼吸道合胞病毒引起的肺损伤。
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6
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8
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10
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