A case report demonstrates that a novel mutation discovered in the junctional plakoglobin (JUP) gene can lead to lethal congenital epidermolysis bullosa (EB).
The report, titled “A Novel Mutation in Junctional Plakoglobin Causing Lethal Congenital Epidermolysis Bullosa,” was published in The Journal of Pediatrics.
The normal structure and function of organs, such as the skin and the heart, depend on a variety of things, including the spatial location of cells and the interaction between cells. Cell adhesion, which refers to the physical connection between cells, is important for cell communication, which in turn is necessary for proper cell functioning.
A desmosome is a structure by which two adjacent cells are attached. One of the proteins important for the formation of a desmosome is called plakoglobin.
Mutations affecting the plakoglobin protein can lead to a variety of diseases, the most severe of which is lethal congenital epidermolysis bullosa. In this disease, patients show severe skin fragility and loss of skin integrity, which is usually followed by death.
The study reports the case of a newborn boy presented to doctors at a New York hospital on the first day of birth for skin desquamation (skin peeling), alopecia totalis (complete loss of hair), and nail dystrophy (misshapen, damaged nails). Based on the symptoms, physicians suspected a diagnosis of either infection, immunodeficiency, metabolic disease, or genetic disorders associated with skin fragility.
Test results, however, showed no bacterial organisms or viral DNA.
Despite the fact that the healthcare professionals used fragile skin care protocols, the infant continued to develop new skin erosions. Doctors then suspected the baby of having a skin fragility disorder with a defect in desmosomal proteins.
The potential known disorders that would cause these signs include lethal acantholytic epidermolysis bullosa epidermolytic ichthyosis, ectodermal dysplasia-skin fragility syndrome, or lethal congenital epidermolysis bullosa.
Researchers then conducted whole-exome sequencing (WES), which is a technique that is used to determine mutations in a patient’s DNA. WES revealed that there was a mutation in the JUP gene, which resulted in the production of a shorter plakoglobin protein and compromising its proper function.
The child died at day 18 after birth. An autopsy was performed and showed that while the gastrointestinal tract was normal, the heart was small and had an atrial septal defect and the infant’s lungs showed mild fibrosis. There was also infection of Enterobacter cloacae complex and Escherichia coli in the lung and heart tissues.
This case report demonstrates a novel and particularly damaging mutation in the JUP gene, which leads to skin fragility, early cardiac fibrosis, and neonatal death.
The team also emphasized the relevance that WES had in this clinical case. “Expedited genetic testing enabled diagnosis while the patient was in the neonatal intensive care unit, providing valuable information for the clinicians and family,” the researchers wrote.
“The expectation is that more services based on these and other high-throughput technologies will become readily available to patients and the wider population,” the clinical team concluded.