[Cohen syndrome in a child caused by compound heterozygous variants in VPS13B gene]

Area of Science:

• Genetics
• Molecular Biology
• Ophthalmology
• Pediatrics

Background:

• Cohen syndrome (CS) is a rare genetic disorder characterized by developmental delay, intellectual disability, distinct facial features, and early-onset hypotonia.
• Progressive vision loss and neutropenia are significant clinical manifestations that can impact patient management and prognosis.
• Accurate and timely diagnosis of CS is essential for appropriate genetic counseling and potential therapeutic interventions.

Purpose of the Study:

• To present a case of a pediatric patient with Cohen syndrome (CS) and highlight the diagnostic process.
• To investigate the molecular basis of CS in this patient, focusing on variants in the VPS13B gene.
• To emphasize the utility of integrated molecular pathogenicity assessment for improving early diagnostic accuracy in CS.

Main Methods:

• Clinical evaluation of a 7-year-old girl presenting with progressive vision loss, developmental delay, and neutropenia.
• Genetic testing to identify variants in the VPS13B gene.
• Molecular pathogenicity analysis, including RNA expression studies (reverse transcription quantitative polymerase chain reaction) and bioinformatic analysis to assess variant impact.

Main Results:

• The patient was diagnosed with Cohen syndrome (CS) due to compound heterozygous variants in the VPS13B gene: c.6940+1G>T and c.2911C>T.
• The c.6940+1G>T variant was shown to cause exon 38 skipping, leading to a frameshift and premature termination of the VPS13B protein.
• Significantly reduced VPS13B gene expression (P<0.05) and bioinformatic predictions indicated the production of truncated proteins from both identified variants.

Conclusions:

• This case underscores the importance of a comprehensive diagnostic approach for Cohen syndrome (CS).
• Integrating clinical findings with detailed molecular analyses (DNA, RNA, and protein level) significantly enhances the accuracy and timeliness of CS diagnosis.
• Early and precise diagnosis facilitates better patient management and genetic counseling for families affected by Cohen syndrome.