An unbalanced 5;12 translocation in a patient with septo-optic-dysplasia

Document Type



Paediatrics and Child Health


Introduction: Septo optic dysplasi is a congenital defect of midline and forebrain. The etiology of SOD is considered multifactorial, though familial cases have been reported with mutations in homeobox genes (HESX1, SOX 2, SOX 3).Here we report a patient with septo optic dysplasia and an unbalanced 5;12 translocation.
Case report: An 11-year-old girl with global develop-mental delay and congenital anomalies was referred for a second opinion. Clinical examination was significant for short stature, abnormal head shape, mid face hypoplasia and dysconjugate eye movements with visual impairment. Brain MRI showed absence of the septum pellucidum and small optic apparatus compatible with SOD. Array comparative genomic hybridization revealed a terminal duplication from5q35.1 to 5qter and a terminal deletion from 12pter to12p13.32. FISH studies confirmed maternally inherited unbalanced 5;12 translocation.
Discussion: This translocation lead to duplication of 77and deletion of 22 genes on chromosome 5 and 12 respectively. Of the genes that are deleted from chromosome 12;three (WNT5B, ERC1, FBXL14) have been reported to be important for brain development. WNT5B encode secreted signaling proteins important for patterning during embryo-genesis. The protein encoded by the ERC1 gene is involved in the activation of NF-kB, a transcription factor playing arole in apoptosis and development. Protein encoded by theFBXL14 gene interacts with ubiquitination targets important in development. We propose that haploinsufficiency of these genes might be disrupting the prosencephalon development resulting in the phenotype of septo optic dysplasia. These genes warrant further investigations for their role in prosencephalon development.


This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Annals of Neurology