Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• SOX2 gene mutations are linked to ocular anomalies and pituitary dysfunction.
• Understanding the spectrum of SOX2 defects is crucial for diagnosis and management.

Purpose of the Study:

• To identify and characterize SOX2 abnormalities in patients with ocular and/or pituitary dysfunction.
• To investigate the functional consequences of identified SOX2 mutations.
• To explore genotype-phenotype correlations in affected individuals.

Main Methods:

• Molecular analysis of SOX2 in nine patients.
• Identification of mutations (missense, nonsense, frameshift) and submicroscopic deletions.
• In vitro transactivation assays using the HESX1 promoter.
• Clinical evaluation of ocular anomalies and associated complications.

Main Results:

• SOX2 abnormalities were found in nine patients, including novel mutations and deletions.
• Deletions involved Alu repeats, suggesting a mechanism for genomic rearrangement.
• Mutations resulted in SOX2 proteins with significantly reduced or absent transactivation activity.
• All patients presented with ocular anomalies; some had additional complications like arachnoid cysts.

Conclusions:

• SOX2 defects are diverse, encompassing various mutations and Alu repeat-mediated deletions.
• There is significant phenotypic variability in SOX2-related disorders.
• No clear correlation exists between residual SOX2 activity and clinical severity, indicating complex disease mechanisms.