目的 对12例Loeys-Dietz综合征(LDS)患者的临床表征及基因变异谱进行总结分析，探讨LDS基因变异类型与临床表型的潜在相关性。 方法 选取2015年1月至2022年1月于首都医科大学附属北京安贞医院疑诊为LDS的12例患者为研究对象。收集患者的相关临床资料，提取患者外周血基因组DNA并进行基因检测，对候选变异进行致病性分析。 结果 12例LDS患者临床表型主要涉及心血管、骨骼肌肉、颅面、皮肤、眼部等多系统体征。4例患者(患者5-1、5-2、6、7)均携带TGFBR1基因杂合错义变异，5例患者(患者1-1、1-2、2、3、4)均携带TGFBR2基因杂合变异，2例患者(患者8-1、8-2)均携带TGFB3基因杂合移码变异，1例患者(患者9)携带SMAD3基因杂合错义变异。其中TGFBR1基因c.603T>G(p.1201M)及TGFB3基因c.536delA(p.H179fs35)变异均未见报道。 结论 LDS主要与TGFBR1、TGFBR2、SMAD3、TGFB2、TGFB3及SMAD2基因变异相关，同一变异位点所致疾病临床表型严重程度可能不一，不同变异位点所致疾病临床表型特异。 Objective To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. Methods Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. Results The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c. 603T>G (p.1201M) andTGFB3 c. 536delA (p.H179FS35) had not been reported previously. Conclusion Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Abstract
Objective To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. Methods Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. Results The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c. 603T>G (p.1201M) andTGFB3 c. 536delA (p.H179FS35) had not been reported previously. Conclusion Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
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