Summary of Medical Research

KDM1A or LSD1 is an important gene in the field of epigenetics, as it was the first known histone demethylase. This means that it has a key role in regulating other genes. In plain English – it has a systemic influence over a person’s development, and is highly preserved down to basic organisms like the zebrafish. Mutations on this gene seem to have a significant impact and there is a growing body of medical research focused on better understanding this dynamic. The majority of known mutations appear to be de novo (spontaneous/not inherited).

In part thanks to this website, there is an increasing population of KDM1A/LSD1 patients globally (over two dozen as of the Summer of 2023). MyGene2 has been able to capture profiles of some of these patients and is a great resource for learning more about the patient population. Since this is such a fast and growing group, we have found that Wikipedia and other sources do not always have the most current information on the disorder. If you are a new patient family, please consider creating an anonymous profile on MyGene2, which will help with research efforts on this gene! Below is a recent screenshot of KDM1A profiles on MyGene2, including details on the variant type, actual cDNA change, and resulting protein change. The more profile data we have, the more researchers can generate insights on the impact these mutations have.

The first medical paper on human KDM1A/LSD1 mutations was published in the American Journal of Medical Genetics in May 2014. This paper posited that KDM1A could be the source of developmental delays in the featured patient. However, since the featured patient was the first KDM1A case in the medical literature, the authors also mentioned that an ANKRD11 mutation could have also been a contributor. Since then, we have learned that the ANKRD11 mutation is unlikely to have had much impact and the KDM1A mutation is likely the key driver behind the patient’s development delays.

The second medical paper on human KDM1A/LSD1 mutations was published in Genetics in Medicine in December 2015. At this time, there were three known KDM1A patients. The paper noted that social networking is a powerful strategy to discover genes for rare Mendelian conditions. The authors were the developers of MyGene2, a web-based repository that enables families, clinicians and researchers to search for gene matches based on analysis of phenotype and exome data.

The third medical paper on human KDM1A/LSD1 mutations was published in Human Molecular Genetics in April 2016. It analyzes the effects of KDM1A mutations in three patients on the structure, stability and activity of LSD1 using both in vitro and cellular approaches. The paper concludes that these mutations lead to a partial impairment of catalytic activity, and perturb the ability of LSD1 to engage transcription factors that influence development. These effects indicate the relevance of LSD1 in gene regulation and organism development.

There is other research in progress and we will update this website as it is released. If you know of a researcher who is interested in epigenetics and/or KDM1A/LSD1, please put them in touch with us! Since this gene was the first known histone demethylase, there is quite a bit of interest in it. We are always happy to assist in any way on future research projects! By building our tribe and our knowledge of this disorder, we can collaborate more effectively and truly help our kids be the best that they can be.

Links to Referenced Medical Research Papers:

  1. Paper from American Journal of Medical Genetics
  2. Paper from Genetics in Medicine
  3. Paper from Human Molecular Genetics