基于二代测序技术的矮小症患者表型与基因型研究

Study on phenotype and genotype of short stature based on second-generation sequencing technology

摘要:

目的：应用二代测序技术结合临床总结矮小症患者的基因型和表型特点。方法：收集2015年5月至2020年5月就诊于重庆医科大学附属儿童医院内分泌遗传代谢科、符合矮小症标准的患者资料，收集患者临床表型并利用二代测序技术分析患者基因型。结果：175例患者中81例检出致病性或可能致病性基因突变，检出率为46.29%；检出46个单基因突变、10个拷贝数变异、2个基因印记异常和1个染色体异常；发现29个尚未报道过的变异位点。本队列中综合征性矮小患者基因突变阳性率更高，身材矮小伴骨片异常、骨骼畸形、特殊面容、性发育异常、发育迟缓的患者具有分子病因的可能性更大。结论：二代测序技术有助于明确矮小症患者的分子病因，在分子水平扩展临床医生对矮小症患者基因型和表型的认识。

Abstract:

Objective：To summarize the genotypic and phenotypic characteristics of patients with short stature based on the clinic feature and second-generation sequencing technology. Methods：Patients met the criteria of short stature were included in study who visited the Department of Endocrinology and Genetic Metabolism，Children’s Hospital of Chongqing Medical University from May 2015 to May 2020. The phenotypes of the patients were collected and the genotypes of patients were analyzed by second-generation sequencing technology. Results：The study included 175 patients，of which 81 were found pathogenic or likely pathogenic gene mutations，with a detection rate of 46.29%；there were 46 single gene mutations，10 copy number variations，2 gene imprinting abnor－malities and 1 chromosome abnormality；29 unreported mutation sites were found. The gene diagnosis rate of patients with syndromic short stature was higher in this cohort，and the patients with short stature，accompanied with bone X-ray abnormality，bone deformity，special face，sexual development disorder and stunting were more likely to have genetic etiology. Conclusion：The second-generation sequencing technology is helpful to clarify the genetic etiology of patients with short stature and expand clinicians’ understanding of genotype and phenotype of patients with short stature at molecular level.