The past and future of genetics in pulmonary disease: You can teach an old dog new tricks.
The past and future of genetics in pulmonary disease: You can teach an old dog new tricks.
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肺部疾病遗传学的过去和未来：你可以教老狗新把戏。
DOI：
10.1002/ppul.24669
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发表时间：
2020
影响因子：
3.1
通讯作者：
Hamvas,Aaron
中科院分区：
文献类型：
--
作者：
Nogee,LawrenceM;Hamvas,Aaron
长期以来，儿科肺科医生通过护理囊性纤维化(CF)儿童，将遗传学的进步融入到他们的日常实践中。早在1938年，多萝西·安德森就提出了遗传性遗传病的遗传基础和隐性遗传模式。即使在没有已知基因缺陷的情况下，鉴定可靠的生物标志物--汗水氯化物--也可以确定诊断，而汗液测试仍然是当今CF诊断的重要组成部分。1989年对Cf基因的鉴定是一项里程碑式的成就--通过位置测绘和测序完成，这些方法后来被更快、更具成本效益的方法所取代。随着对CFR基本缺陷的识别，突变蛋白生物学的了解，以及研究突变蛋白的体外工具的发展，现在已经开发出药物来挽救CFTR功能，这可能会改变CF治疗的性质。人类基因组计划和随后的基因组技术的快速扩展提供了对疾病潜在机制的更深层次的理解，并加强了对已知和未知疾病的诊断方法。因此，儿科肺科医生现在越来越多地面临新的遗传性疾病，或者是非侵入性诊断疾病的能力，这些疾病以前主要是通过相关的肺组织病理学来定义的，需要肺活检才能诊断。例如，表面活性物质代谢的遗传性障碍导致一系列疾病，从新生儿呼吸衰竭到成人发作性肺纤维化(1-7)。与肺表面活性物质功能障碍相关的肺组织病理学诊断是多种多样的，包括肺泡蛋白沉积症、脱屑性间质性肺炎、婴儿期慢性肺炎、非特异性间质性肺炎和普通性间质性肺炎。表面活性物质紊乱突出了两个要点：1)不同基因的致病变异可能表现为相似的临床或组织病理表型；2)同一基因的突变可能表现为不同的表型表达，甚至在家庭内也是如此，这也表明遗传背景和环境暴露对表型的表达起着作用。这些观察提出了关于如何定义疾病的根本问题，无论是基于临床、影像或肺组织病理学，还是基于潜在的机制-随着儿童肺部疾病新的遗传机制的发现，这一难题将更频繁地发生。
Pediatric Pulmonologists have long incorporated advances in genetics into their every-day practice through their care of children with cystic fibrosis (CF). First described in 1938 by Dorothy Anderson, the genetic basis and recessive inheritance pattern of CF was recognized early on. The identification of a reliable biomarker–sweat chloride-allowed for establishing the diagnosis, even in the absence of the known genetic defect, and the sweat test remains an essential component of CF diagnosis today. The identification of the CF gene in 1989 was a landmark achievement–accomplished through positional mapping and sequencing using methods that have since been supplanted by faster and more cost-effective approaches. The identification of the basic defect in CF, an understanding of the biology of the mutated protein, and development of in vitro tools to study mutated proteins has now led to the development of drugs to rescue CFTR function that are likely to transform the nature of CF treatment.The Human Genome Project and the subsequent rapid expansion of genomic technology has provided deeper understanding of underlying mechanisms of disease and enhanced the approaches to diagnosis for both recognized and unknown disorders. Thus, pediatric pulmonologists are now increasingly faced with new genetic disorders, or the ability to noninvasively diagnoses disorders that were previously defined largely by their associated lung histopathology and required lung biopsies for diagnosis. As an example, genetic disorders of surfactant metabolism result in a spectrum of disease from neonatal respiratory failure to adult onset pulmonary fibrosis (1-7). The lung histopathology diagnoses associated with surfactant dysfunction disorders is variable, and includes diagnoses referred to as pulmonary alveolar proteinosis, desquamative interstitial pneumonia, chronic pneumonitis of infancy, non-specific interstitial pneumonia, and usual interstitial pneumonia. The surfactant disorders highlight two important points: 1) pathogenic variants in different genes may manifest with a similar clinical or histopathologic phenotype; and 2) mutations in the same gene may manifest with variable phenotypic expression, even within families, also suggesting that genetic background and environmental exposures play a role in the expression of phenotype. These observations raise fundamental questions concerning how to define disease, whether based on clinical, imaging, or lung histopathology or the underlying mechanism–a conundrum that will occur more often as new genetic mechanisms for childhood lung disease are uncovered.
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影响因子：
6.2
作者：
Tarter,RE;Switala,JA;Arria,A;Plail,J;VanThiel,DH
通讯作者：
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长期酗酒者的认知丧失和恢复。
影响因子：
--
作者：
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DOI：
--
发表时间：
1983
期刊：
影响因子：
--
作者：
J. Saunders;Roger Williams
通讯作者：
Roger Williams
影响因子：
1.9
作者：
ALLEN, RP;WAGMAN, A;MCINTOSH, M
通讯作者：
MCINTOSH, M
肝脏疾病中的脑电图。
DOI：
--
发表时间：
1957
期刊：
The Lancet
影响因子：
--
作者：
B. Parsons;W. Summerskill;A. Dawson;S. Sherlock
通讯作者：
S. Sherlock