Clinical AreaGynaecology

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

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The hereditary causes of gynaecological and obstetric diseases are clarified by means of molecular genetic diagnostics. 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 female reproductive system. The heredity patterns of such diseases are the basis of genetic counselling for patients, persons at risk and affected families. In the last 30 years, several hundred genes have been characterized which cause gynaecological/obstetric disorders or contribute to the development of such disorders. Current research results have a direct bearing on the diagnostic procedure in the laboratory and genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable, hereditary diseases (mutations at least eleven different genes can lead to hereditary breast cancer [“locus heterogeneity”]). On the other hand, different mutations in one and the same gene BRCA1 lead to clinically more or less clearly distinguishable disease entities (familial breast cancer vs. Fanconi anaemia [“allelic heterogeneity”]).

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

• monogenic diseases (autosomal or X-chromosomal inheritance)
• digenic diseases, which only manifest themselves when mutations are simultaneously present in heterozygous state in two different genes. The two normal gene products together form functional heterodimers. Digenic inheritance is involved in ~3% of hereditary diseases in addition to the classic autosomal and X-linked diseases.
• mitochondrial diseases (maternal or autosomal inheritance)
• multifactorial diseases (interaction of several to many genes plus environmental factors)

Congenital malformations in gynaecology often appear sporadically - is there a genetic (co-)cause? Several hundred inherited gynaecological/obstetric disorders are demonstrably based on genetic changes and lead to disorders due to changes in the proteins that build up the female organism and affect its reproductive functions. 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 panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using the Sanger technique. Some of the more common groups of diseases are listed below.

In the majority of diseases in female development, one or more genetic factors are causally involved in the causal pathogenesis of a developmental disorder (see e.g. 46XX gonadal dysgenesis, Mayer-Rokitansky-Küster-Hauser syndrome and Müller-Gang persistence). Often numerical and structural chromosomal defects are detectable, as well as sometimes gene mutations that cause monogenically inherited syndromes (e.g. the relatively common Fragile X syndrome). Diagnostic gene panels for developmental disorders sometimes comprise a large number of genes that are sequenced in parallel, while initially, only those genes that appear associated with the clinical picture are analyzed. The individual gene panels can be used separately or in combination for different diagnostic purposes.

In most families only single cases of breast or ovarian cancer occur. In familial breast and/or ovarian cancer, genetic mutations are often found to be the cause. Carriers of the gene mutation have increased risks of developing breast or ovarian cancer at some point in time. The risks of disease depend on the gene mutation. Depending on the family constellation, genetic examinations of the risk genes for breast / ovarian cancer are offered. There is a 10% probability of finding the right gene in the molecular genetics laboratory. Defined inclusion criteria concern the number of women with breast cancer in the family, their age at first diagnosis, women with ovarian cancer, men with breast cancer etc. etc. For these and other cancers, the heredity patterns are well known, and the genetic defects are in many cases directly detectable by means of differently composed gene panels. An additional gene panel is available for endometrial carcinoma, in which susceptibility genes have also been taken into account.

In cases of sterility, a woman will not become pregnant despite regular intercourse for >1 year, primary sterility is present if the woman has never been pregnant before. In the case of infertility, the woman can become pregnant but cannot continue to full term. One third of infertility is caused by the woman or the man or by both partners. The most common causes are tubal infertility, anatomical obstacles to pregnancy or primary and secondary ovarian insufficiency. Corresponding to the manifold causes, the molecular genetic diagnostic spectrum is also broad with regard to hormone-related disorders and anatomical causes. Depending on the clinical findings, various more or less comprehensive gene panels are used.