Kingsmore Panel Analysis: Genetic Screening for Successful Family Planning

It is common knowledge that not all children are born healthy. However, only a few couples know their personal risk of becoming a sick child. 2–4% of children suffer from genetic disorders that can only be identified with the help of a detailed genetic test, whereas 20% of parents are carriers of a genetic disorder unbeknownst to them. A child is especially at risk if both parents are carriers of a defect gene so that the child inherits it from both of them. This is called a recessive hereditary disease.

Can you determine a predisposition for a genetic disease before getting pregnant? The answer is yes: there are genetic tests available to establish the risk of over 400 genetic diseases. The tests are done using blood samples of the parents-to-be.

Can a couple have healthy kids if both parents are carriers of a genetic disease? That is possible. In this case, genetic counselling and prenatal diagnostics is recommended.

If you’d like to know whether you and your partner have a predisposition for a genetic disease, you can contact JUNISA to get genetic testing performed. The test and evaluation of results will take place at the Medical Genetics Centre in Munich. Following the test, the doctors of the Centre will advise you on further procedures. All stages of test processing can be tracked using a special online system.

What is a recessive hereditary disease?

Recessive diseases make up for a large percentage of hereditary disorders in children. There are currently over 1,000 known recessive diseases. A prompt diagnosis of such illnesses (which are often serious) significantly improves the prognosis if preventive measures and therapy are administered early on.

Recessive diseases are disorders in which a phenotype is only expressed when both copies of a gene are damaged or have mutated. This means that a genetic error must as a rule be inherited from both parents in order for an illness to manifest itself in the next generation. Healthy parents that have a mutation in only one gene copy (heterozygous carriers) pass the recessive disease on to their children with a probability of 25%. If the genetic error is inherited from one of the parents only, the child too becomes a heterozygous carrier of the recessive disease. It has the genetic error, but does not develop the disease or any of its symptoms.

Autosomal recessive diseases are caused by genetic defects on non-sex chromosomes (autosomes). X-chromosomal recessive inheritance affects almost exclusively men, since the disease-relevant gene is located on the X chromosome and cannot be compensated for by a gene copy on the second X chromosome because a man does not have it. Sons of women who are carriers of an X-chromosomal disorder are 50% likely to be affected by the disease itself. The daughters of female carriers have a 50% risk of becoming carriers too.

Statistically, there is a 2.8% average likelihood of getting a recessive gene mutation that could lead to a serious childhood disease (Bell CJ et al., 2011, Sci Transl Med 3:65). Blood relatives have a common ancestor and therefore share more genes, which increases the risk of genetic recessive diseases for their children.

The carrier status is usually established using heterozygous screening (Kingsmore Panel analysis). This procedure is performed with the help of a new DNA sequencing technique known as „Next Generation Sequencing“ and allows to detect a variety of autosomal recessive diseases, as well as analyse 447 disease-relevant genes — which, if mutated, are responsible for 448 recessive diseases.

The Kingsmore Panel analysis is a sensible diagnostic measure if, based on the clinical phenotype of the child, it is no longer possible to narrow the diagnosis down. In addition, genetic screening is highly effective in establishing the likelihood of a hereditary disease before conception. This is especially important if there is an elevated risk of a severe recessive disorder in the family — for instance, undefined genetic maladies and/or consanguine parents. Taking a test that uses the Kingsmore Panel to determine recessive diseases can be a decisive step in family planning.