Stumpf Max Jonathan, Schaefer Christian Alexander, Mahn Thorsten, Wolf Anna Elisabeth, Biener Leonie, Hendig Doris, Nickenig Georg, Schahab Nadjib, Pizarro Carmen, Skowasch Dirk
Department of Internal Medicine II, Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany.
Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine Westphalia, University Hospital of the Ruhr University Bochum, Bad Oeynhausen, Germany.
Intractable Rare Dis Res. 2022 Feb;11(1):7-14. doi: 10.5582/irdr.2021.01162.
Pseudoxanthoma elasticum (PXE) is a rare, heritable disease caused by various, mainly recessively transmitted mutations in the gene. Due to calcification of soft connective tissue phenotypic hallmarks are progressive loss of vision, alternation of the skin and early onset atherosclerosis. Beside these main features patients also suffer from impaired alveolar diffusion. The present study focused on impaired lung functioning based on a large cohort of patients with PXE, its long-term development, and genotype-phenotype correlation. Retrospectively, 98 patients and 45 controls were enrolled. All patients underwent body plethysmography and carbon monoxide diffusion testing. Of 35 patients three or more body plethysmographic records were available for long-term analysis. For genotype-phenotype analysis genotypes were grouped as two missense, mixed, or two nonsense mutations. Patients with PXE showed significantly reduced vital capacity ( < 0.05), diffusion capacity ( < 0.01), and diffusion transfer coefficient ( < 0.05). Over a mean period of 38 months diffusion capacity ( < 0.05) and diffusion transfer coefficient ( < 0.01) dropped significantly whereas lung volumes remained unchanged. Genotype-phenotype correlation revealed no connection between gene variants and lung functioning. In conclusion, PXE is accompanied by progressive reduction of alveolar diffusion indicating progressive alterations of lung tissue. Genotype-phenotype correlation with genotypes sorted as missense and nonsense mutations do not explain impaired lung functioning.
弹性假黄瘤（PXE）是一种罕见的遗传性疾病，由该基因的各种主要隐性遗传突变引起。由于软结缔组织钙化，其表型特征为视力逐渐丧失、皮肤改变和早发性动脉粥样硬化。除了这些主要特征外，患者还存在肺泡弥散功能受损。本研究基于一大群PXE患者，重点关注肺功能受损情况、其长期发展以及基因型与表型的相关性。回顾性地纳入了98例患者和45例对照。所有患者均接受了体容积描记法和一氧化碳弥散测试。35例患者中有3份或更多份体容积描记记录可用于长期分析。对于基因型-表型分析，基因型被分为两个错义突变、混合突变或两个无义突变。PXE患者的肺活量（<0.05）、弥散能力（<0.01）和弥散转移系数（<0.05）显著降低。在平均38个月的时间里，弥散能力（<）0.05）和弥散转移系数（<0.01）显著下降，而肺容积保持不变。基因型-表型相关性显示基因变异与肺功能之间没有关联。总之，PXE伴有肺泡弥散的逐渐降低，表明肺组织发生了渐进性改变。将基因型分类为错义突变和无义突变的基因型-表型相关性并不能解释肺功能受损的情况。
