A highly complex system, which proceeds in several stages, is involved in the development of the heart. The DNA provides the according genetic code. After this “blueprint” has been deciphered, highly diverse and complicated biochemical processes that are all linked to each other start running in the embryo’s somatic cells like in a clockwork. Many of these are not understood in detail yet. We do know, however, that alterations in the maternal or paternal genetics have the potential to disturb the coded blueprint in such a way as to make it impossible for the cell to process the information contained by said blueprint. Such cases lead to organ malformations.

Finding out what Goes Wrong

Hypoplastic left heart syndrome (HLHS) is one of these organ malformations. It is distinguished by an underdeveloped left heart chamber. This rare malformation is among the most severe congenital heart malformations. If left untreated, it results in the unborn child’s death. Improving the treatment for this disease requires finding out more about the specific gene mutations that interfere with the organ development during the embryonic stage; furthermore, we need to find out what causes them and which biochemical processes go wrong in the cells, thus affecting the genetic activity.

First Findings Thanks to Donated Samples from the Register

We have now initiated a large bioinformatic analysis of available exome sequencing data in order to find answers to these questions. The study is based on technological advancements in this method and first findings regarding gene mutations involved in HLHS. In this context, the samples patients, their siblings and parents have donated to the National Register play a crucial role.

What Can Be Assumed

We know today that congenital heart disease has many diverse causes. Besides gene mutations, these also include so-called epigenetic factors such as, for instance, biochemical processes within the cells that interfere with the genes’ activity. Basically, everything points to the idea that only an interaction of several genes with rare mutations is able to lead to the described maldevelopment of the heart. Our research is aimed at identifying the genetic profile that interferes with the biochemical processes involved in organ development.

Precise Prognoses, Improved Treatment

Our bioinformatic analysis of the data sequenced from the donated samples will help us to detect new and yet undetected gene mutations that are disease-relevant. These include single nucleotide variations (SNVs), insertions and deletions (INDELs) and copy number variations (CNVs). In doing so, we will be able to visualize the gene-network of this congenital heart malformation step by step. This is important to be able to investigate the complex inheritance pattern that is behind the rarely occurring HLHs. It is our biggest hope that prognoses regarding the heart function are able to be made on the basis of such a genetic profile in the future; and that this leads to the development of new treatment methods.