Clinical and pathological features and varied mutational spectra of pathogenic genes in 55 Chinese patients with nephronophthisis

Clin Chim Acta. 2020 Jul:506:136-144. doi: 10.1016/j.cca.2020.03.015. Epub 2020 Mar 12.

Abstract

Background: Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease (ESRD) in children. This study was performed to explore the pathogenic gene mutations and clinical and pathological features of Chinese patients with NPHP.

Methods: Patients for whom causative mutations were not identified in our previous study, as well as those recruited later, were subjected to whole-exome next-generation sequencing (NGS) or the exome of 63 primary cilia disease genes.

Results: We recruited 55 patients (27 boys and 28 girls) from 48 families, mainly from South China. We subjected 35 patients to NGS. Disease-causing mutations were revealed in seven more families (nine patients) by NGS. In total, disease-causing mutations were identified in 25 patients from 19 families, accounting for 39.6% (19/48) of all families, and novel mutation rate was 77.8% (35/45). NPHP1 and NPHP3 mutations were identified in 14.6% (7/48) and 12.5% (6/48) of all families, respectively. The patient with CEP83 mutations presented with prominent glomerular cysts and glomeruli dysplasia without extrarenal involvement.

Conclusion: A high novel mutation rate was identified, and disease-causing mutations of NPHP3 prevailed in this group of Chinese NPHP patients. This is the second report of a patient with CEP83 mutations.

Keywords: CEP83; Mutations; Nephronophthisis; Next-generation sequencing.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Asian People
  • Child
  • Child, Preschool
  • Computational Biology
  • Cytoskeletal Proteins / genetics*
  • Female
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney Diseases, Cystic / congenital*
  • Kidney Diseases, Cystic / genetics
  • Kinesins / genetics*
  • Male
  • Mutation

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • NPHP1 protein, human
  • nephrocystin-3, human
  • Kinesins

Supplementary concepts

  • Nephronophthisis, familial juvenile