Characteristics of the test: (includes 2 genes)

HNF1β (OMIM #189907)

PAX2 (OMIM #167409)

General characteristics of the clinical phenotype

The congenital anomalies of the kidney and urinary tract (CAKUT) is a heterogeneous group of conditions, usually diagnosed in childhood. It comprises of malformations such as renal agenesis, dysplasia and hypoplasia, vesicoureteral reflux, etc. CAKUT are quite common – they account for 20-30% of all malformations diagnosed prenatally and may explain the majority of chronic and terminal renal failure in both children and adults.

CAKUT result from problems in the embryonic development of the genitourinary tract. They are characterised with great variability of clinical presentation – there are many cases described in the literature where individuals carrying the same pathogenic variant develop very different symptoms, from severe malformations incompatible with life, to minimal changes in renal structure and function, diagnosed in adulthood. This phenomenon has been observed even among individuals within the same family. The phenotypic variability observed in CAKUT is often explained with the modifying effect of other genes or genetic variants. This notion is supported by the identification of individuals with more than one pathogenic mutation. All this justifies the classification of CAKUT as multifactorial disorder. 

Two genes, mutations in which are commonly associated with CAKUT, particularly renal hypodysplasia, are HNF1β (also known as TCF2) and РАХ2. Between 5% and 15% of the patients with these malformations harbour HNF1β or РАХ2 pathogenic variant. That is why, screening these two genes for mutation is the usual first step in the genetic testing for CAKUT patients.

Reasons for referring: 

All patients with congenital anomalies of the kidney and urinary tract.

Interpretation of results:

• Identification of point mutations and small deletions/insertions in HNF1β and PAX2 will lead to genetic diagnosis and will help the clinical team to choose the best suited treatment for you or your child;

• Mutations in HNF1β are associated with an increased risk of maturity onset diabetes of the young, type 5 (MODY5). The fact that a person carries a pathogenic variant is an indication for routine prophylaxis as means for early diagnosis and successful therapy;

• Our genetic counsellor will interpret the result for you and will answer any questions you may have.

Method: Sanger sequencing (ABI 3130xl).

The method involves bidirectional DNA sequencing of all coding exons and intron-exon boundaries of the HNF1β и PAX2.

Since the most common pathogenic variants in HNF1β are deletions/duplications encompassing several exons of the gene, we recommend that the present test is combined with Test №92.

For patients where the present test does not reveal the molecular basis for the disorder, we recommend next generation sequencing of a panel of 212 genes, associated with CAKUT (Test № 91).

The laboratory offers single exon sequencing for establishing the carrier status of close relatives of patients with known HNF1β or PAX2 mutations (Test № 128).

Sensitivity of the method: 99.5%

What does the test involve? 

• DNA isolation and sample storage.

• Direct sequencing of target genes / gene regions to detect pathogenic mutations.

• Preparation of written result from the genetic test.

• Diagnostic interpretation of the results and genetic counselling.

Biological material: Venous blood of DNA

For more information, please read "Biological Sample Requirements and Transport Information" carefully.