title: A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.
abstract: Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.
authors.affiliation: Paediatric Endocrinology Unit, "Cardarelli" Hospital, Campobasso, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Macchiaroli
authors.affiliation: Ulverscroft Vision Research Group, Developmental Biology Unit, UCL Institute of Child Health, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kelberman
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Napoli, Italy.
authors.forename: Renata Simona
authors.initials: RS
authors.lastname: Auriemma
authors.affiliation: NE Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Drury
authors.affiliation: Ulverscroft Vision Research Group, Developmental Biology Unit, UCL Institute of Child Health, London, UK.
authors.forename: Lily
authors.initials: L
authors.lastname: Islam
authors.affiliation: Paediatric Endocrinology Unit, "Cardarelli" Hospital, Campobasso, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Giangiobbe
authors.affiliation: Paediatric Endocrinology Unit, "Cardarelli" Hospital, Campobasso, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ironi
authors.affiliation: NE Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lench
authors.affiliation: Ulverscroft Vision Research Group, Developmental Biology Unit, UCL Institute of Child Health, London, UK.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Sowden
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Napoli, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Napoli, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University "Aldo Moro", Bari, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cavallo
authors.affiliation: Department of Medicine and Health Sciences, Section of Endocrinology, University of Molise, Campobasso, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasperi
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University "Aldo Moro", Bari, Italy. Electronic address: mariafelicia.faienza@uniba.it.
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
mesh_terms: D000293:Adolescent; D000853:Anophthalmos / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics*; D006579:Heterozygote; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000209:etiology / Q000235:genetics*; D008297:Male; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019382:Human Growth Hormone
keywords: ACTH; FSH; GH; GHD; GHRH; GnRH; Growth hormone deficiency; HMG; Hypogonadotropic hypogonadism; Hypopituitarism; LH; MRI; SOX2 mutations; SRY-related high mobility group; TRH; TSH; adrenocorticotropic hormone; follicle-stimulating hormone; gonadotropin releasing hormone; growth hormone; growth hormone deficiency; growth hormone releasing hormone; luteotropin hormone; magnetic resonance imaging; thyroid-stimulating hormone; thyrotropin releasing hormone