A new, rare syndrome linked to mutations in the MAP3K20 gene has been identified
In a recent article published in Human Genetics, a research team identified genetic variants (mutations) in the MAP3K20 gene that cause malformations in the hands and feet, hearing loss, and abnormalities in nails or muscles. Until now, these changes had only been associated with cases where both gene copies were affected (known as homozygosity). However, this study examines de novo mutations (which appear for the first time in a person, as they arise during embryonic development) in a single copy of the MAP3K20 gene (heterozygosity) and describes how these mutations impact health.
The article describes five individuals with different clinical features, such as craniosynostosis (a condition where the skull bones fuse prematurely), limb malformations, hearing loss, and symptoms resembling ectodermal dysplasia (a disorder affecting the skin, nails, hair, and glands). These patients exhibit both common symptoms and unique manifestations, highlighting the complexity of the disorder.
The team suggests that these mutations may disrupt a biological process called the endothelial to mesenchymal transition, which is crucial for early body development. This could explain the observed symptoms. The discovery broadens the range of health issues associated with MAP3K20 gene mutations and underscores the need for continued research to better understand its role in early human development.
Laia's story
Laia played a key role in the discovery of this disease. This five-year-old girl from Girona came to Sant Joan de Déu Barcelona Children's Hospital just months after she was born, seeking a diagnosis and treatment for the syndactyly (fusion of fingers or toes) she exhibited. The medical team conducted various tests to assess the extent of the condition and to determine if other organs were affected. They also performed several genetic studies on both her and her parents.
However, Laia’s condition had never been described before, which made the diagnosis challenging. Three years ago, the Sant Joan de Déu Genetics Department reached out to researchers at Baylor College of Medicine (Houston, Texas), who were researching the MAP3K20 gene. Through this collaboration, they were able to identify five patients with the same mutation and similar symptoms.
So far, Laia is the only child in Spain diagnosed with this disease, and globally, there are known cases of a 10-year-old boy, a 14-year-old adolescent, and two young adults, aged 18 and 27.
