Unraveling and Expanding the Genotypic Spectrum of Kabuki Syndrome with Identification of de Novo Protein-Truncating Mutations in the KMT2D Gene: Insights into the Role of Premature Stop Codons in the Etiology of the Disorder

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Kabuki Syndrome (KS) is a rare, multisystem congenital disorder with five foremost clinical manifestations encompassing dysmorphic facial characteristics, postnatal growth constraint, craniofacial/skeletal anomalies, mild to moderate intellectual disability, and dermatoglyphic abnormalities. We analyzed two unrelated Iranian patients suspected of having KS using whole-exome sequencing. An in silico analysis was performed to evaluate the potential effects of the discovered variants on the structure and function of the corresponding protein. A novel de novo heterozygous protein-truncating mutation was found in patient 1, NM_003482.4: c.13818C>G (p.Y4606X), and a de novo heterozygous premature stop codon was identified in patient 2, NM_003482.4: c.16360C>T (p.R5454X). These mutations cause haploinsufficiency in KMT2D and are absent in the proband’s parents. Although these mutations provide evidence of the potential pathogenicity of KMT2D in KS, further functional studies are necessary to confirm their impact. Our observations not only provide evidence for the potential pathogenicity of the two identified protein-truncating mutations but also have important implications for the accurate diagnosis and potential treatment of KS. These findings underscore the significance of genetic testing in diagnosing this disorder and expand our understanding of the role of KMT2D mutations in its pathogenesis.

This publication has 28 references indexed in Scilit: