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Kidney Week

Abstract: FR-PO973

Clinical Characteristics of HNF1B Related Disorders in Japanese Population

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • Morisada, Naoya, Department of Clinical Genetics, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan
  • Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • Iijima, Kazumoto, Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • Minamikawa, Shogo, Kobe University Graduate School of Medicine, Kobe, Japan
Background

Hepatocyte nuclear factor 1β (HNF1B) gene is located at chromosome 17q12 and is known as the causative gene for the renal cysts and diabetes syndrome (RCAD). It is also well known that various phenotypes of congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome shows multi-system disorders as well as RCAD.

Methods

We conducted gene screening for cases with RCAD, CAKUT and Bartter-like syndrome cases. As a result, 31 cases were detected heterozygous variants or whole gene deletions in HNF1B (heterozygous variant: 18 cases and deletion: 13 cases). All cases with deletion were diagnosed with 17q12 deletion syndrome confirmed by MLPA or array CGH. A retrospective review of clinical data was conducted for these cases.

Results

Most cases had morphological abnormalities in the renal urinary tract system. Diabetes developed in 11 cases (38%). Hyperuricemia and hypomagnesemia were associated with 5 cases (17%) and 12 cases (41%), respectively. Pancreatic malformations were detected in 6 cases (21%). Nine patients (31%) had liver abnormalities. When data were classified by mutation types, the eGFR (estimated glomerular filtration rate) levels were significantly lower in the patients who carried heterozygous variants compared with those in the patients who carried deletions (median: 37.9 ml/min/1.73 m2 vs 55.9 ml/min/1.73 m2, p=0.0264). Patients who carried deletions had higher frequencies of hypomagnesemia (p=0.0005) and neurological complications (p=0.0064) than those who carried variants.

Conclusion

We presented the clinical characteristics of HNF1B related disorders. To predict the renal prognosis or onset of extra renal complications, accurate genetic diagnosis at an early age is important. HNF1B related disorders show various clinical symptoms and should be noted for accurate diagnosis.