摘要目的:探讨2个Joubert综合征家系的临床特征与遗传学病因。方法:选取2020年11月27日、2021年1月22日于河南省人民医院就诊的2个Joubert综合征家系为研究对象。分析2个家系的临床特征，采集先证者及其家系成员外周血样，提取基因组DNA，进行高通量基因测序分析，应用Sanger测序对致病变异位点进行验证，并对家系2高危胎儿进行产前诊断。结果:家系1先证者为胎儿，宫内孕23 +5周，超声及磁共振均表现为"小脑蚓部发育不良"及"臼齿征"，引产胎儿无明显临床表型异常，基因检测提示其 INPP5E基因存在c.812+3G>T和c.1828G>C复合杂合变异，临床诊断为Joubert综合征1型。家系2先证者表现为生长发育迟缓、智力低下、有特殊面容、肌张力低下、右足六趾畸形，磁共振提示小脑发育不良及"臼齿征"，先证者 ARMC9基因存在c.485C>G和c.1878+1G>A复合杂合变异，临床诊断为Joubert综合征30型。产前诊断提示家系2胎儿 ARMC9基因携带c.485C>G杂合变异，新生儿随访临床表型正常。 结论:INPP5E基因c.812+3G>T及c.1828G>C复合杂合变异和 ARMC9基因c.485C>G及c.1878+1G>A复合杂合变异分别是家系1和家系2的遗传学致病原因，上述发现扩展了Joubert综合征的致病变异谱，为遗传咨询和产前诊断提供了依据。

abstractsObjective:To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome.Methods:Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2.Results:The proband of pedigree 1 was a fetus at 23 + 5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign" . No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c. 812+ 3G>T and c. 1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign" . The proband was found to harbor c. 485C>G and c. 1878+ 1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c. 485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. Conclusion:The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.