ESPE Abstracts (2014) 82 P-D-1-3-186

A Boy with Septo-Optic Dysplasia Identified a Mutation in WDR11

Hirohito Shimaa, Yoko Izumib, Ikumi Umekia, Akimune Kagaa, Miki Kamimuraa, Akiko Saito-Hakodaa, Junko Kannoa, Maki Fukamib & Ikuma Fujiwaraa


aDepartment of Pediatrics, Tohoku University School of Medicine, Sendai, Japan; bDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan


Background: Septo-optic dysplasia (SOD) is a rare disorder characterized by optic nerve hypoplasia, anterior midline abnormality and pituitary hormone deficiency. Mutations of several genes are known to cause SOD related condition, such as HESX1, SOX2, SOX3, and OTX2, but mutations of WDR11 has not been reported in SOD.

Objective: Reporting the first SOD patient identified a mutation in WDR11.

Method: Genomic DNA was extracted from the patient, and 30 genes related to congenital hypopituitarism were screened by the Haloplex method (Agilent Technologies) on a MiSeq next generation sequencer (Illumina). The mutation indicated by the screening analysis was verified by Sanger sequencing.

Case report: A 2-year-old boy suffered from hypoglycemia, dysopia, and mental retardation. Laboratory data showed low serum IGF1 (23 ng/ml) and low free T4 (0.69 ng/dl). We performed TRH test (peak TSH was 17.44 μcIU/ml at 120 min and peak PRL was 89.15 ng/ml at 30 min), CRH test (peak ACTH was 68.2 pg/ml at 15 min and peak cortisol was 10.5 μcg/ml at 30 min), GRF test (peak GH was 13.60 ng/mL at 60 min), and arginine stimulation test (peak GH was 5.28 ng/ml at 90 min). A brain MRI confirmed pituitary hypoplasia, agenesis of anterior corpus callosum, and deficit of optic chiasm. We diagnosed him as SOD with combined pituitary hormone deficiency, and the hypoglycemic episodes were disappeared after the replacement therapy with hydrocortisone, L-thyroxine and GH.

Results: We identified a heterozygous missense mutation in WDR11 (p.A1076T). The analyses of the family members are currently underway.

Discussion and conclusion: This is the first case reporting a WDR11 mutation in SOD patients. WDR11 was reported to interact with a transcription factor EMX1, and this protein–protein interaction, which was a part of the Sonic-Hedgehog-Patched-Gli signaling pathway, might lead to the malformation of hypothalamus.

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