Characteristics of the test: (includes 1 gene)

HNF1β (OMIM #189907)

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.

One of the genes most commonly affected by mutations associated with CAKUT is  HNF1β (also known as TCF2). The majority of the pathogenic variants affecting its sequence are deletions/duplications encompassing multiple exons.

Reasons for referring: 

All patients with congenital anomalies of the kidney and urinary tract, especially if renal hypodysplasia and/or family history of MODY5 are present.

 Индикация за провеждане на изследването за генетични варианти в HNF1β са наличието на бъбречна хиподисплазия и/или фамилна история на диабет тип MODY 5.

Интерпретиране на резултатите:

• Identification of deletions/insertions in HNF1β 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: MLPA (Multiplex Ligation-Dependant Probe Amplification)

MLPA analysis is a semi-quantitative method for determining DNA copy numbers. It is applied when screening for intragenic or whole gene deletions of duplications. SALSA MLPA P241 MODY mix 1 на MRC-Holland (Amsterdam, Holland) is used for identification of large deletions/duplications in HNF1β.

Since the same clinical presentation may result from point mutations in HNF1β and PAX2, if  no genetic changes are identified using MLPA, we recommend that a direct sequencing is applied for screening the entire coding sequence of these two genes, Test № 90.

Sensitivity of the methods: 90%

What does the test involve? 

• DNA isolation and sample storage.

• MLPA for detection of deletions/duplications affecting HNF1β.

• 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.