Physicians
As Rudolf Virchow first proposed, the origin of any clinically diagnosed pathology is the cell (cellular pathology). This is reflected in the cell-specific gene expression regulated by a cell-specific networking of the associated genes, also called signal pathways or genetic networks. Not every mutation of a given DNA reference sequence (see www.emsbl.org) directly leads to a clinically detectable pathology. Therefore, many clinical syndromes with male or female infertility are expressed in different ways.
Well-known examples are androgen resistence syndromes (database: http://ww2.mcgill.ca/androgendb/) and the congenital aplasia of the vas deferens (CBAVD) which are often but not always associated with the somatic disease cystic fibrosis (home.arcor.de/ttm-toby/muko.htm; www.genet.sickkids.on.ca/cftr/)
In general terms, we can estimate that the number of genes influencing human fertility directly or indirectly ranges between 3000 and 5000. They can roughly be divided into three groups:
- Genes expressed in the germ line only
- Genes expressed in the gonads and
- Genes active during ontogenesis, e.g. during imprinting and implantation in early embryogenesis.
The last group of genes is the main reason why reproductive physicians practising modern methods of artificial fertilisation are now raising critical questions about the risk of transmitting the genetically induced infertility of the couple to their progeny or of inducing somatic pathologies which were not detectable in the parents.
From the view of a scientist engaged in basic genetic research, it would therefore be imperative to perform a causal genetic diagnosis for patients´ infertility directly with the male and female germ cells. During the routine clinical care this is of course only possible if the invasive sampling of germ line tissue or germ cells will have a medical indication.
Therefore, molecular genetic and cytogenetic diagnosis of male or female infertility generally starts in the lab with collecting DNA and RNA samples and chromosomes from the patients´ leukocytes. These can be isolated much more easily than germ cells by taking a blood sample from the patient. For DNA/RNA diagnosis,
20 ml whole blood must be sent to the lab in an EDTA tube.
Sending the blood sample to the lab for diagnosis of the AZF loci or gene mutations causing probably the patient´s POF syndrome must be accompanied by a patient questionnaire describing all clinical data and including letter copies of the findings.