Clinical AreaUrology

Here you will find the disease-related gene panels available for the clinical area specified above.

If you cannot find the disease you are looking for, please use a known synonym in the search (also in English).

Molecular genetic diagnostics are also used to clarify the hereditary causes of urological diseases. The aim here is to detect deviations from the reference genome (wild type) and then, if necessary, to distinguish between neutral variants and pathogenic mutations that are important for the physiological development and undisturbed functioning of the urogenital system. The inheritance patterns of urological-genetic diseases represent the basis of genetic counselling for patients, persons at risk and affected families.

In the last 30 years many genes have been characterized which cause urological diseases or contribute to the development of urological disorders. Current results of urogenetic research have a direct impact on the diagnostic procedure in the laboratory and genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable, hereditary forms of XX and XY gonadal dysgenesis (locus heterogeneity). On the other hand, different mutations in one and the same CLCN5 gene lead to clinically apparently clearly separable disease entities (Dent's disease, hypophosphatemic rickets, nephrolithiais type 1 and/or low-molecular proteinuria with hypercalciuric nephrocalcinosis; allelic heterogeneity).

Formal genetically and etiologically, the following groups of urological diseases can be distinguished:

• monogenic diseases (autosomal or X-chromosomal inheritance)
• mitochondrial diseases (maternal or autosomal inheritance)
• multifactorial diseases (interaction of several to many genes plus environmental factors)

Congenital malformations of the urogenital system often appear sporadically - is there a genetic (co-)cause? Several hundred inherited urological disorders are proven to be based on genetic changes and lead to disorders in the proteins that build up the urogenital system. DNA diagnostics therefore often involves a step-by-step procedure in which the most frequent mutations are first tested before the very rare genetic causes are also identified in parallel approaches using extensive and cost-intensive gene panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using Sanger technology. Some of the more common disease groups are listed below.

In urology, in the majority of diseases one or more genetic factors are causally involved in the causal pathogenesis of the developmental disorder. Sometimes numerical and structural chromosome defects are detectable as well as mutations that cause monogenic syndromes (e.g. androgen insensitivity syndrome). Diagnostic gene panels for developmental disorders comprise up to several dozen genes, which are sequenced in parallel. Initially, only those genes that appear primarily associated with the clinical picture are analysed. The individual gene panels can be used separately or in combination for the diagnostic purposes.

Sterility and infertility affect ~15% of couples in Germany and Europe, and causal pathogenetics can be elucidated in about the same proportion of both sexes. After the exclusion of cytogenetic causes, the differential diagnosis of infertility often starts with targeted single gene sequence analyses. In many cases, however, only extended panel examination with numerous genes allows the exact genetic diagnosis to be established. In addition to the genes for primary ovarian insufficiency and for several rare syndromes in both sexes, dozens of other genes are characterised in the respective panels, which also pertain to hormonal disorders, for example. For the monogenic causes of infertility, the inheritance patterns are precisely known and the genetic defects are directly detectable.

Although the causal pathogenesis of renal cysts can often be considered as monogenic in the simplest sense, be it following autosomal recessive or autosomal dominant inheritance, other genes are available in the corresponding panels in addition to the main genes (PKD1, PKD2 and PKHD1). On the other hand, it seems immediately obvious that various forms of nephrolithiasis are generally based on multifactorial genesis, so that single-gene diagnostics cannot be used as the primary method of diagnosis. Hence comprehensive gene panels are offered here as well.

With the important exception of von Hippel-Lindau syndrome, practically all other malignant tumor diseases in urology are not simply caused monogenic. Accordingly, panels with susceptibility genes are offered for prostate and renal (cell) carcinoma, for example, as well as gene combinations which, according to the latest findings, are significantly involved in the multifactorial tumor process. Depending on the preliminary clinical findings as those for e.g. prostate carcinoma, analyses of the genetic preconditions may also be included for therapy options in the respective gene panels.