A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes

Pediatr Diabetes. 2020 May;21(3):422-430. doi: 10.1111/pedi.12959. Epub 2020 Jan 29.


Background/objectives: Patients referred for HNF1B testing present very heterogeneous phenotypes. Despite suggestive characteristics, many do not harbor mutations in HNF1B. Our objective was to evaluate the clinical characteristics of probands referred for HNF1B genetic testing through a nationwide monogenic diabetes screening program.

Methods: Probands tested for HNF1B mutations in the 2005-2018 period (N = 50) were identified in the Polish Monogenic Diabetes Registry, which prospectively recruits primarily pediatric patients and their families on a nationwide scale. Variants that had been reported pathogenic were reassessed using criteria of the American College of Medical Genetics and Genomics (ACMG). A structured medical interview was performed with all available individuals, their parents, and/or their physicians. For each patient, HNF1B score was calculated based on available clinical information.

Results: The study group numbered 36 unrelated probands (28% lost to follow-up): 14 with pathogenic or likely-pathogenic variants in HNF1B, one with a variant of uncertain significance, and 21 negative for HNF1B mutations. Presence of cystic kidneys (OR = 9.17, 95% CI:1.87-44.92), pancreatic abnormalities (OR = 15, 95% CI:1.55-145.23), elevated liver enzymes (OR = 15, 95% CI:1.55-145.23) best discriminated HNF1B-positive cases from the negative ones. Presence of impaired glucose tolerance coupled with kidney disease in the proband and one parent was also highly predictive for HNF1B mutations (OR = 11.11, 95% CI:1.13-109.36). HNF1B-score with recommended cutoff distinguished patients with and without HNF1B findings with 100% sensitivity and 47.6% specificity. Addition of four clinical variables to select patients based on HNF1B score improved specificity to 71.4% (95% CI:47.8%-88.7%) while retaining 100% sensitivity.

Conclusions: Detailed medical interview may enable more accurate patient selection for targeted genetic testing.

Keywords: MODY; cystic kidneys; diabetes mellitus; genetic testing; phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Diseases / diagnosis*
  • Central Nervous System Diseases / epidemiology
  • Central Nervous System Diseases / genetics
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Dental Enamel / abnormalities*
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Infant
  • Kidney Diseases, Cystic / diagnosis*
  • Kidney Diseases, Cystic / epidemiology
  • Kidney Diseases, Cystic / genetics
  • Male
  • Middle Aged
  • Mutation
  • Patient Selection
  • Poland / epidemiology
  • Referral and Consultation / statistics & numerical data
  • Young Adult


  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta

Supplementary concepts

  • Mason-Type Diabetes
  • Renal cysts and diabetes syndrome