TSC2/PKD1邻接基因综合征的临床特征及遗传学分析:病例系列研究OACSTPCD

Background TSC2/PKD1 contiguous deletion syndrome(PKDTS)is caused by the deletion of TSC2 gene and PKD1 gene,which has been rarely reported in China.Objective To summarize the clinical phenotype and genetic characteristics of 5 cases with PKDTS.Methods Clinical data about five children with PKDTS from 2015 to 2023 in Chinese PLA General Hospital and Provincial Hospital Affiliated to Shandong First Medical University were collected and analyzed retrospectively.Peripheral blood of the patients and their parents were collected for genetic testing.Different molecular biology methods,such as whole exome sequencing,gene panel,whole genome sequencing,long segment PCR,Sanger sequencing and multiplex ligation-dependent probe amplification,were used for gene testing.Results Five patients with PKDTS all started with epilepsy,had similar clinical characteristics,including skin leukoplakia,intracranial nodules,polycystic kidney,renal dysfunction,hypertension,etc.,accompanied by varying degrees of developmental delay,which fused the phenotypes of tuberous sclerosis(TSC)and autosomal dominant polycystic kidney disease(ADPKD).Rapamycin could control TSC related epilepsy well,and patients with severe polycystic kidney disease could use tovastatin and fluid extraction+drug coagulation surgery to alleviate symptoms.The results of genetic testing showed that 5 children had TSC2/PKD1 gene deletions in different length and regions:Case 1,chr16:133.18 kb missing in the 2131595-2264778 region;Case 2,TSC2 gene exon 31-42 and PKD1 gene exon 30-46 were missing,with a length of 17.64 kb;Case 3,chr16:g.2114201-2185990 area had a missing length of 71.789 kb;Case 4,chr16:2125441-2176668 region had a deletion of copy number 51.22 kb;Case 5,16p13.3(16:2099825-2151077)region were missing,covering 51.25 kb.Conclusion A summary of 5 PKDTS cases shows no significant correlation between the location and length of gene deletions and the severity of clinical symptoms.The use of whole genome sequencing can accurately diagnose PKDTS in the early stage and intervene.Rapamycin combined with anti-epileptic drugs can effectively control TSC related epilepsy.