We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities.
- Authors
Suzuki, Junichi; Azuma, Noriyuki; Dateki, Sumito; Soneda, Shun; Muroya, Koji; Yamamoto, Yukiyo; Saito, Reiko; Sano, Shinichiro; Nagai, Toshiro; Wada, Hiroshi; Endo, Akira; Urakami, Tatsuhiko; Ogata, Tsutomu; Fukami, Maki
- 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.
- Subjects
GENETIC mutation; PHENOTYPES; HUMAN genetic variation; EYE diseases; PITUITARY diseases; STATISTICAL correlation; IN vitro studies; PATIENTS
- Publication
Journal of Human Genetics, 2014, Vol 59, Issue 6, p353
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1038/jhg.2014.34