ESPE Abstracts (2015) 84 P-1-87

aPediatric Sections, Department of Biomedical Sciences and Human Oncology, University of Bari ‘Aldo Moro’, Bari, Italy; bMedical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca’ Granda Hospital, Milan, Italy; cDepartment of Surgery and Translational Medicine, Eye Clinic, University of Florence, Florence, Italy

Background: OTX2 is expressed in the human brain and plays a key role in the eye development. OTX2 mutations are reported in patients with ano/microphtalmia, optic nerve or optic chiasm hypoplasia, ocular coloboma and retinal dystrophies, associated in some cases with brain or pituitary abnormalities.

Objective and hypotheses: Most of OTX2 mutations are nonsense or frameshift, more rarely missense mutations occur.

Method: We describe a child with microphtalmia and GH deficiency carrying a novel OTX2 heterozygous mutation.

Results: At birth, she presented right microphtalmia, absence of retinal vascularization, vitreal spots and optic nerve hypoplasia in the right eye and mild macular dystrophy in the left eye. Electroretinogram and p-VEP confirmed the right nerve hypoplasia. A brain MRI showed normal midline structures and cerebral parenchyma, mild hypoplasia of the anterior corneal segment, dysmorphic cristalline with increased posterior convexity and thin optical nerve in the right eye. Left nerve eye was normal. When 20 months old, after excluding other causes of microphtalmia, OTX2 gene sequencing was performed and showed a heterozygous c.402del mutation. At the age of 3.8 years, height was −2.1 SDS (TH −0.6 SDS), BMI-1.0 SDS, bone age 3 years. Routine biochemistry was normal as well as thyroid and adrenal function, while GH peaks after arginine and clonidine test were 5.24 and 3.46 ng/ml respectively. IGF1 level was 47.5 (10th-25th). Recombinant GH treatment was started (33 mcg/kg per day).

Conclusion: In this paper we report on a novel OTX2 heterozygous mutation (c.402del), never described before, in a patient with microphtalmia and growth hormone deficiency. This frameshift mutation (p.S135Lfs*43) causes a premature codon stop 43 amino-acids downstream which is predicted to generate a premature truncation and thus a non-functional protein. Parental analysis indicated that the mutation was absent from the healthy parents (de novo mutation). Follow-up to evaluate furtehr pituitary deficiency is ongoing.

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