摘要目的:分析探讨罕见的2型Treacher Collins综合征（Treacher Collins Syndrome 2，TCS2）家系的临床特征、分子病因学特征及治疗手段。方法:完善先证者（女，8岁）的病史采集、体格检查、实验室检查、听力学检查及影像学检查，完善先证者家属的体格检查，同时提取先证者的基因组DNA进行全外显子组测序，提取家系成员基因组DNA进行一代测序验证，并检索PubMed、中国知网等数据库，对截止2023年8月31日前报道的由 POLR1D基因致病变异所致的TCS2临床特征进行归纳总结并分析比较。 结果:先证者自幼听力差，纯音测听示传导性听力损失；下颌较小，双侧耳前瘘管及杯状耳畸形；颞骨CT示左侧外耳道、双侧中耳及内耳畸形；手术植入骨导助听装置，术后听力恢复至正常水平；其母亲下颌略小。先证者 POLR1D基因存在新的变异NM_015972.4：c.38_47del，为杂合变异，常染色体显性遗传，变异遗传自其母亲，根据美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics，ACMG）指南评级为致病变异。已报道病例的回顾性分析未发现TCS2的基因型-表型相关性。 结论:分子诊断对TCS2患者的诊断意义重大，面部形态正常者也有可能是 POLR1D 基因致病变异携带者，有生育出完全外显TCS2患儿的风险，适时的骨导助听装置干预能提高患者的生活质量。

abstractsObjective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.