Prenatal diagnosis of dent disease type I with a nonsense pathogenic variant in CLCN5: a case study

BMC Med Genomics. 2024 Jan 24;17(1):34. doi: 10.1186/s12920-024-01809-7.

Abstract

Introduction: Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians.

Methods: A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis.

Results: No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features.

Conclusion: This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

Keywords: CLCN5 gene pathogenic variant; Dent disease; Foetus; Prenatal diagnosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosome Aberrations
  • Chromosomes, Human, X
  • Dent Disease*
  • Female
  • Genetic Testing
  • Humans
  • Pregnancy
  • Prenatal Diagnosis