Diagnosis and genotype-phenotype correlation in patients with PKD1/TSC2 contiguous gene deletion syndrome

Clin Nephrol. 2022 Jun;97(6):328-338. doi: 10.5414/CN110476.

Abstract

Deletions involving the TSC2 and PKD1 genes lead to tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD), which is known as TSC2-PKD1 contiguous gene deletion syndrome (PKDTS). PKDTS leads to severe symptoms and death. There are few reported cases of PKDTS, the phenotypic descriptions are poor, and detailed statistics and descriptions of the time of onset and prognosis of PKDTS are lacking. This is the first study to report on the clinical data of PKDTS patients in China. We analyzed all cases including Chinese individuals and summarized the clinical manifestations and genetic characteristics. Our study was the first to use a combination of exome sequencing and multiplex ligation-dependent probe amplification (MLPA) to screen and diagnose PKDTS. We found that many PKDTS patients have the following: multiple renal cysts; angiofibromas (≥ 3) or fibrous cephalic plaque; subependymal nodules; seizures; intellectual disability. PKDTS develops into polycystic kidney disease from before birth to 17 years old and the time of occurrence of end-stage renal disease or dialysis was 21.62 ± 12.87 years of age, which was significantly earlier than in ADPKD caused by PKD1 mutation. Compared with non-Chinese individuals of diverse ancestry, Chinese people have significant differences in the clinical characteristics, including ungual fibromas (≥ 2), and shagreen patch. Five novel large deletions were identified in Chinese. We found no relationship between the clinical phenotype and the genotype. We combined exome sequencing with MLPA to develop a diagnostic method for PKDTS.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Gene Deletion
  • Genetic Association Studies
  • Humans
  • Mutation
  • Polycystic Kidney, Autosomal Dominant* / diagnosis
  • Polycystic Kidney, Autosomal Dominant* / genetics
  • Polycystic Kidney, Autosomal Recessive* / genetics
  • TRPP Cation Channels / genetics*
  • Tuberous Sclerosis
  • Tuberous Sclerosis Complex 2 Protein / genetics*
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • TRPP Cation Channels
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • polycystic kidney disease 1 protein

Supplementary concepts

  • Polycystic kidneys, severe infantile with tuberous sclerosis