Diagnostic Challenges in a Family with Dominant Dystrophic Epidermolysis Bullosa and Isolated Hereditary Nail Disorder: Paternal Gonosomal Mosaicism for COL7A1 Mutation and Maternal RSPO4 Variant.

ABSTRACT

Dystrophic epidermolysis bullosa (DEB) has long been recognized as a well-known genodermatosis, caused by COL7A1 gene pathogenic variants. Isolated anonychia associated with RSPO4 gene mutation is a recently described non-syndromic autosomal recessive condition. In this family, a 13-year-old girl presented with severe epidermolysis bullosa symptoms. Family history revealed milder but similar complaints in the siblings, and anonychia affecting all nails in the mother and maternal relatives. The father did not have any signs of DEB. Genetic testing revealed heterozygous c.6127G>A (p.Gly2043Arg) variant in the COL7A1 (NM_000094.4) gene, in the proband and her affected siblings. The variant was not detected in the mother or father, prompting investigation into parental mosaicism. Detection of the variant in sperm sample suggested paternal mosaicism. Additionally, RSPO4 gene (NM_001029871.4) was sequenced in the mother and two of her affected sisters for suspected non-syndromic isolated anonychia, revealing homozygous c.79+1G>A variant. Isolated nail disease in the mother was initially thought to be the result of DDEB nails-only subtype and the DEB in the children was inherited from the mother. However, further clinical and genetic investigation showed that the condition in the patient and her siblings arose from gonosomal mosaicism in the father and the nail phenotype in the mother is a separate coincidental condition. This report aims to serve as an example for similar cases and highlight the importance of detailed genetic analysis guided by comprehensive medical history in reaching a diagnosis.