Moritz Herkner, Christina Rapp, Simon Y Graeber, Charlotte Marx, Carlotta Rambuscheck, Simone Reu-Hofer, Nagehan Emiralioglu, Nural Kiper, Alexandru I Gilea, Ilenia Notaroberto, Enrico Baruffini, Bettina Temmesfeld-Wollbrück, Christoph Klein, Han Wen, Mirjam Stahl, Matthias Griese, Florian Gothe
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引用次数: 0
摘要
目的：我们报告了两例携带新型c.644C b> T . l215p变异的双等位基因C-C趋化因子受体2型（CCR2）缺乏症患者，他们在婴儿期出现慢性呼吸道症状，并在儿童期出现多发性弥漫性囊性病变。方法：采用全外显子组测序对患者进行诊断，并在原代患者细胞中对该变异进行功能验证。结果：虽然囊肿的大小和范围多年来保持稳定，但分别在青春期和成年期出现进行性肺功能下降。发现CCR2 p.L215P变体表达缺失，患者单核细胞在CCR2配体C-C基序配体2 （CCL2）刺激下表现出迁移缺陷。结论：通过长达25年的随访，本报告扩展了我们对CCR2缺乏症肺部疾病的理解，并提供了囊性肺病的另一种单基因病因。对受影响个体的早期遗传诊断可能允许通过造血干细胞移植进行潜在的治愈性治疗。
Multicystic Interstitial Lung Disease Due to a Novel Biallelic C-C Chemokine Receptor Type 2 Variant.
Objective: We are presenting two individuals with biallelic C-C chemokine receptor type 2 (CCR2) deficiency carrying the novel c.644C>T p.L215P variant, who presented with chronic respiratory symptoms during infancy and developed multiple diffuse cystic lesions during childhood.
Methods: The patients were diagnosed by means of whole exome sequencing and functional validation of the variant was performed in primary patient cells.
Results: While size and extent of the cysts were stable over years, progressive lung function decline was noted in adolescence and adulthood respectively. The CCR2 p.L215P variant was found to be loss-of-expression and patient monocytes displayed a migration defect upon stimulation with the CCR2 ligand C-C motif ligand 2 (CCL2).
Conclusion: With a follow-up of up to 25 years, this report expands our understanding of lung disease in CCR2 deficiency and offers another monogenic cause of cystic lung disease. Early genetic diagnosis of affected individuals might allow potentially curative treatment by haematopoietic stem cell transplantation.
期刊介绍：
Pediatric Pulmonology (PPUL) is the foremost global journal studying the respiratory system in disease and in health as it develops from intrauterine life though adolescence to adulthood. Combining explicit and informative analysis of clinical as well as basic scientific research, PPUL provides a look at the many facets of respiratory system disorders in infants and children, ranging from pathological anatomy, developmental issues, and pathophysiology to infectious disease, asthma, cystic fibrosis, and airborne toxins. Focused attention is given to the reporting of diagnostic and therapeutic methods for neonates, preschool children, and adolescents, the enduring effects of childhood respiratory diseases, and newly described infectious diseases.
PPUL concentrates on subject matters of crucial interest to specialists preparing for the Pediatric Subspecialty Examinations in the United States and other countries. With its attentive coverage and extensive clinical data, this journal is a principle source for pediatricians in practice and in training and a must have for all pediatric pulmonologists.
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