Related Experiment Video
Updated: Apr 30, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities
Junichi Suzuki1, Noriyuki Azuma2, Sumito Dateki3
11] National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan [2] Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
Abstract:
Multiple mutations in SOX2 have been identified in patients with ocular anomalies and/or pituitary dysfunction. Here, we identified SOX2 abnormalities in nine patients. The molecular defects included one missense, one nonsense and four frameshift mutations, and three submicroscopic deletions involving SOX2. Three of the six mutations and all deletions were hitherto unreported. The breakpoints determined in one deletion were located within Alu repeats and accompanied by an overlap of 11 bp. Three of the six mutations encoded SOX2 proteins that lacked in vitro transactivation activity for the HESX1 promoter, whereas the remaining three generated proteins with ∼15-∼20% of transactivation activity. All cases manifested ocular anomalies of various severities, together with several complications including arachnoid cyst and hamartoma. There was no apparent correlation between the residual activity and clinical severity. The results indicate that molecular defects in SOX2 are highly variable and include Alu repeat-mediated genomic rearrangements. Our data provide further evidence for wide phenotypic variation of SOX2 abnormalities and the lack of genotype-phenotype correlation in patients carrying SOX2 lesions.
Insights
Genetic defects in SOX2 cause various ocular and pituitary issues. This study reveals diverse SOX2 mutations and deletions, highlighting variable disease severity and no clear genotype-phenotype correlation.
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.
Related Concept Videos
01:33Pleiotropy
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...