目的 对1例临床疑似为Loeys-Dietz综合征(LDS)的患者行全外显子组测序，明确其遗传学病因。 方法 将1例2018年9月就诊于首都医科大学附属北京安贞医院的患者作为研究对象，完善其临床资料及既往病史。采集患者及父母的外周血样，对其进行全外显子组测序，重点分析与遗传性主动脉瘤疾病相关的基因。并通过Sanger测序对候选变异进行家系验证。 结果 患者临床检查及既往病史均提示存在早发性主动脉扩张及夹层等心血管异常，临床疑似为LDS。二代测序发现其TGFBR2基因存在c.1526G>T(p.Gly509Val)杂合错义变异，其父母未携带相同变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为疑似致病变异(PM1+PM2_Supporting+PM6+PP3+PP4)。 结论 TGFBR2基因c.1526G>T变异可能是该患者的遗传学病因，国内既往未见报道。上述结果丰富了LDS患者TGFBR2基因的变异谱，为患者的临床诊断和遗传咨询提供了依据。 Objective To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). Methods A child who was presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. Results The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c. 1526G>T missense variant of theTGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+ PM2_Supporting+ PM6+ PP3+ PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). Conclusion The TGFBR2 c. 1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of theTGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.
Abstract
Objective To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). Methods A child who was presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. Results The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c. 1526G>T missense variant of theTGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+ PM2_Supporting+ PM6+ PP3+ PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). Conclusion The TGFBR2 c. 1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of theTGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.
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