Format

Send to

Choose Destination
Nephrol Dial Transplant. 2015 May;30(5):835-42. doi: 10.1093/ndt/gfu370. Epub 2014 Dec 13.

Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract.

Author information

1
Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
2
Department of Human Genetics, UZ Leuven/KU Leuven, Leuven, Belgium.
3
Department of Sociology, Vrije Universiteit Brussel, Brussels, Belgium.
4
Neonatal Intensive Care Unit, UZ Leuven, Leuven, Belgium.
5
Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
6
Department of Nephrology, UZ Leuven, Leuven, Belgium.

Abstract

BACKGROUND:

Congenital anomalies of kidneys and urinary tract (CAKUT) are the most predominant developmental disorders comprising ∼20-30% of all anomalies identified in the prenatal period. Mutations in hepatocyte nuclear factor 1-beta (HNF-1β) involved in the development of kidneys, liver, pancreas and urogenital tract are currently the most frequent monogenetic cause of CAKUT found in 10-30% of patients depending on screening policy and study design. We aimed to validate criteria for analysis of HNF1B in a prospective cohort of paediatric and adult CAKUT patients.

METHODS:

We included CAKUT patients diagnosed in our paediatric and adult nephrology departments from January 2010 until April 2013 based on predefined screening criteria. Subjects presenting with at least one major renal criterion or one minor renal criterion combined with one or more extra-renal criteria in the personal history or a familial history of renal or extra-renal manifestations were considered eligible.

RESULTS:

We prospectively screened 205 patients and detected HNF1B mutations in 10% [n = 20, 12 children, median age 4.2 (range 0-13.1) years and 8 adults, median age 34.8 (range 16.6-62) years]. We observed that bilateral renal anomaly, renal cysts from unknown origin, a combination of two major renal anomalies and hypomagnesaemia were predictive for finding HNF1B mutations (P < 0.001; P < 0.001; P = 0.004; P = 0.008, respectively).

CONCLUSIONS:

We demonstrated that HNF1B mutations are responsible for ∼10% of CAKUT cases, both in children and in adults. Based on our results we propose adapted criteria for HNF1B analysis to reduce the screening costs without missing affected patients. These criteria should be reaffirmed in a larger validation cohort.

KEYWORDS:

CAKUT; HNF1β; genetic screening; hepatocyte nuclear factor 1-beta; renal development

PMID:
25500806
DOI:
10.1093/ndt/gfu370
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center