A Rare Case of Congenital Disorder of Glycosylation, Type IIc: Identification of SLC۳۵C۱ Mutation through Whole Exome Sequencing

Abstract: Congenital disorders of glycosylation (CDGs) represent a diverse group of rare genetic diseases characterized by impaired glycan synthesis and attachment to proteins and lipids. CDG Type ۲, specifically caused by mutations in the SLC۳۵C۱ gene, is a relatively newly recognized subtype within this spectrum. This abstract provides an overview of the current understanding of CDG Type ۲, highlighting the diagnostic significance of Whole Exome Sequencing (WES) techniques in identifying SLC۳۵C۱ mutations.Case Presentation: we describe a ۱۲-year-old Female, presented with a complex array of neurological symptoms that began at the age of ۱۰ months. Initially, she experienced recurrent seizures, which were the primary concern for her parents. Over the subsequent years, her condition deteriorated progressively. Notable clinical features included hypotonia, muscle atrophy, severe developmental delays, and microcephaly. Motor milestones were significantly delayed, and her quality of life was profoundly affected. Extensive neurological assessments, imaging studies, and metabolic evaluations were inconclusive, prompting a genomic approach.Methods: In the present study, we ascertained the identity of a patient through clinical studies, including MRI findings and genetics tests. Whole Exome Sequencing (WES) was performed, revealing a previously unidentified heterozygous mutation in the SLC۳۵C۱ gene. This mutation has not been reported in the literature previously and was classified as pathogenic. It encodes a key protein involved in nucleotide sugar transport, which plays a vital role in glycosylation processes within the central nervous system. Subsequently, Sanger sequencing was performed to confirm the causative mutation in twelve members of the patient's family who were diagnosed with autosomal recessive neurodevelopmental disorders. In silico studies, protein structural modeling and docking analyses were conducted using Swiss-model, HOPE, and Phyre-۲ tools.

کلیدواژه ها:

SLC۳۵C۱ ، CDG ، Neurodegenerative ، NGS ، Case report