A novel pathogenic FERMT1 variant in four families with Kindler syndrome in Argentina

Abstract

Background Kindler syndrome is a rare genodermatosis. Major clinical criteria include acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Methods FERMT1 gene was sequenced in 5 patients with a clinical diagnosis of Kindler syndrome. Results We report a novel pathogenic variant detected in four unrelated families of Paraguayan origin, where one nucleotide deletion in FERMT1 gene (c.450delG) is predicted to cause a frameshift mutation leading to loss of function. Haplotype analysis revealed the propagation of an ancestral allele through this population. Conclusions The identification of this recurrent pathogenic variant enables optimization of molecular detection strategies in our patients, reducing the cost of diagnosis.

Infections in Disorders of Immune Regulation

“…The FERMT1 gene encodes proteins involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. FERMT1 deficiency is characterized by recurrent blistering genodermatosis with photosensitivity and progressive poikiloderma known as Kindler syndrome [ 74 ]. Associated mucosal inflammation results in dental caries and gingivostomatitis and makes patients prone to oral candidiasis [ 75 ].…”

“…They also exhibit an increased risk for the development of nonmelanoma skin and oral cancers with considerable phenotypic variability. The precise mechanisms by which FERMT1 deficiency predisposes individuals to these infections may involve compromised immune responses, altered epithelial barrier function, or other immune system abnormalities [ 74 , 75 ].…”

FERMT1 promotes gastric cancer progression by activating the NF-κB pathway and predicts poor prognosis

“…FERMT1 is a newly discovered adhesion protein belonging to the kindlin family, 5 – 7 which consists of Ezrin, Radisin, moesin and a pleckstrin homology domain, and a pleckstrin homology domain. FERMT1 is a mutant gene associated with Kindler syndrome.…”