title: A novel OTX2 gene frameshift mutation in a child with microphthalmia, ectopic pituitary and growth hormone deficiency.
abstract: OTX2 mutations are reported in patients with eye maldevelopment and in some cases with brain or pituitary abnormalities. We describe a child carrying a novel OTX2 heterozygous mutation. She presented microphthalmia, absence of retinal vascularization, vitreal spots and optic nerve hypoplasia in the right eye and mild macular dystrophy in the left eye. Midline brain structures and cerebral parenchyma were normal, except for the ectopic posterior pituitary gland. OTX2 sequencing showed a heterozygous c.402del mutation. Most of OTX2 mutations are nonsense or frameshift introducing a premature termination codon and resulting in a truncated protein. More rarely missense mutations occur. Our novel OTX2 mutation (c.402del) is a frameshift mutation (p.S135Lfs*43), never reported before, causing a premature codon stop 43 amino-acids downstream, which is predicted to generate a premature truncation. The mutation was associated with microphthalmia and ectopic posterior pituitary.
authors.forename: Antonella
authors.initials: A
authors.lastname: Lonero
authors.forename: Maurizio
authors.initials: M
authors.lastname: Delvecchio
authors.forename: Paola
authors.initials: P
authors.lastname: Primignani
authors.forename: Roberto
authors.initials: R
authors.lastname: Caputo
authors.forename: Sara
authors.initials: S
authors.lastname: Bargiacchi
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.forename: Lucia
authors.initials: L
authors.lastname: Mauri
authors.forename: Elena
authors.initials: E
authors.lastname: Andreucci
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
authors.forename: Luciano
authors.initials: L
authors.lastname: Cavallo
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008850:Microphthalmos / Q000150:complications / Q000235:genetics* / Q000473:pathology; D051857:Otx Transcription Factors / Q000235:genetics*; D010900:Pituitary Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: D015415:Biomarkers; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D019382:Human Growth Hormone