title: Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities.
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.
authors.affiliation: 1] 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.
authors.forename: Junichi
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: National Center for Child Health and Development, Department of Ophthalmology and Laboratory of Cell Biology, Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
authors.affiliation: 1] National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan [2] Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Dateki
authors.affiliation: National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Soneda
authors.affiliation: Kanagawa Children's Medical Center, Department of Endocrinology and Metabolism, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.affiliation: Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Saito
authors.affiliation: National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sano
authors.affiliation: Department of Pediatrics, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Pediatrics, Iwata City Hospital, Iwata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Endo
authors.affiliation: Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Urakami
authors.affiliation: 1] National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan [2] Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.affiliation: National Research Institute for Child Health and Development, Department of Molecular Endocrinology, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
mesh_terms: D020087:Alu Elements; D002648:Child; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D056726:Genetic Association Studies; D006065:Gonadotropins, Pituitary / Q000172:deficiency; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D006065:Gonadotropins, Pituitary; C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors