HLHS Cause to Cure

Hypoplastic Left Heart Syndrome Program from Mayo Clinic

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September 16, 2015

Study Finds Possible Genetic Mutation Cause for Hypoplastic Left Heart Syndrome (HLHS)

By suzannerferguson

Here at the Todd and Karen Wanek Family Program for HLHS, our goal is to find a cause to determine a cure. Our researchers have been working tirelessly to find the cause using a wide range of methods looking from imaging, or the study of images, to genetics, the study of genes. Current understanding of the molecular basis of HLHS is limited.


One of our researchers, Dr. Jeanne Theis, recently had her paper entitled, “Compound heterozygous NOTCH1 mutations underlie impaired cardiogenesis in a patient with hypoplastic left heart syndrome” published in Human Genetics. This research study is important because it identifies HLHS-associated gene mutations in a child with HLHS. It is also the first paper in the program to describe the impact of gene mutations using patient-specific pluripotent stem cells. Pluripotent stem cells can be converted into beating heart cells and assessment may enhance the understanding of how gene mutations lead to HLHS.

Researchers were able to identify HLHS-associated mutations in a single gene by looking at the entire genome of each family member. After filtering through millions of variants, they were able to hone in on mutations in the NOTCH1 gene. While they were not looking for a specific gene, NOTCH1 stood out due to an important role it plays in heart development. The study went on to look at stem cells from this patient with HLHS as well as the mother and father. Converting these stem cells to beating heart cells allowed researchers to determine the negative impact the identified NOTCH1 mutations had on heart development. Ultimately, the patient stem cells supported the genetic discovery of NOTCH1 mutations in HLHS.

In summary, the overall findings of the study implicate gene changes as a possible cause of HLHS. The HLHS patient studied has two mutations in the same gene, NOTCH1, whereas the parents each have a single mutation that they pass to the child with HLHS. In the study, one of the mutations in NOTCH1 comes from the mother who has a less severe congenital heart defect. Two mutations in NOTCH1 in the HLHS child compromise both copies of the gene and are associated with the severe congenital heart defect. A single copy of mutated NOTCH1 is not necessarily good news as it may still lead to a less severe congenital heart defect.

Studies such as this one are leading us on the right path in our understanding of HLHS and bring the hope of more advancements in the future.


The Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) is a collaborative network of specialists bonded by the vision of delaying or preventing heart failure for individuals affected by congenital heart defects including HLHS. The specialized team is addressing the various aspects of these defects by using research and clinical strategies ranging from basic science to diagnostic imaging to regenerative therapies.


Tags: gene, genetics, HLHS, HLHS research, NOTCH1, Recent Research, Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome

This is unbelievably exciting news. I always knew in my heart it was genetic. I would believe with my last breath. And yet, I don’t feel “blame” for my child’s illness. I am so happy to know finally something new about single ventricle. This is such great news for all heart families.

Just wanted to home in. Our daughter has HLHS and after our second child was born, he started exhibiting behaviors consistent with Autism. After he was formally diagnosed at 2 yrs old, they tested our sons DNA and it revealed a 7Q 31 Duplication. Then they tested my husband and I and I too have the 7Q31 Duplication. So given that our daughter had HLHS, they tested her and she too has the 7th chromosome duplication. The genetics departments we have worked with have never seen this particular chromosomal variation. Since I have it, when my sister became pregnant, they tested her and she does not have it. So we wish we could afford to test back further like test my parents. But if you ask our family, this duplicated 7th chromosome has “something” to do with her congenital heart defect. I wish we knew where to turn to further investigate what is clearly going on with our family genetically. But I am glad over time they are finding more out about the conditions origins. How awesome it would be if they could find a proactive cute for these kiddos.

I would love to have my 18 yr checked! 8/8/96 I gave birth to Alan Michael he had HLHS and received his wings 9/11/96! One year later I have birth to Austin Lee and he was born with a leaky valve. Five years later we find out my husband had a leaky valve and had to have surgery and in 2009 we almost last him and he’s completely disabled! I would love for Austin to be checked so he would know when he starts to have a family of his own! I don’t want my son to go through what I have! Think this is truly amazing! Austin is Hearty for the #McleanCoHeartWall that is taking place 9/19/15 so very proud of him! Huge blessing and miss Alan Michael everyday

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