Exploring the Genetic Landscape of Knobloch Syndrome: Novel Variant Identification and Literature Review

Knobloch Syndrome (KS) is a rare genetic disorder characterized by ocular abnormalities and central nervous system (CNS) defects, which are attributed to collagenopathy. The primary gene implicated in KS is <i>COL18A1</i>, which encodes the alpha chain of type XVIII collagen. This type of collagen functions as a proteoglycan, predominantly located in the basement membrane of human tissues. This study examined an Iranian female presenting with symptoms of horizontal nystagmus, strabismus, and suspected vision loss, with a potential diagnosis of KS. Genomic DNA was subjected to whole-exome sequencing (WES). The identified pathogenic variant was subsequently confirmed using Sanger sequencing. The impact of the identified pathogenic variant on the structure of <i>COL18A1</i> was assessed using I-TASSER. Analysis of WES data revealed two pathogenic compound heterozygous variants, c.2416C>T (p.Arg806Ter) and c.1698delC (p.Gly567AspfsTer45), in exons 7 and 16, respectively, of the <i>COL18A1</i> (NM_030582) gene. Furthermore, a standard literature review of clinical data highlighted the heterogeneity of phenotypic manifestations, ranging from mild ocular abnormalities to severe neurodevelopmental impairments. This study and literature search offer valuable insights into the genetic landscape of KS, thereby expanding our understanding of the disease and its clinical implications. The identification of novel variants in key genes sheds light on the underlying molecular mechanisms and potential therapeutic targets.