Septo-optic dysplasia caused by a novel FLNAsplice site mutation: a case report

A. Fernández-MarmiesseEmail author View ORCID ID profile,
M. S. Pérez-Poyato,
A. Fontalba,
E. Marco de Lucas,
M. T. Martínez,
M. J. Cabero Pérez and
M. L. Couce

BMC Medical Genetics201920:112

https://doi.org/10.1186/s12881-019-0844-5

Received: 20 July 2018
Accepted: 5 June 2019
Published: 24 June 2019

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Abstract

Background

Septo-optic dysplasia (SOD), also known as de-Morsier syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain including absence of the septum pellucidum and corpus callosum dysgenesis. The variable presentation of SOD includes visual, neurologic, and/or hypothalamic-pituitary endocrine defects. The unclear aetiology of a large proportion of SOD cases underscores the importance of identifying novel SOD-associated genes.

Case presentation

To identify the disease-causing gene in a male infant with neonatal hypoglycaemia, dysmorphic features, and hypoplasia of the optic nerve and corpus callosum, we designed a targeted next-generation sequencing panel for brain morphogenesis defects. We identified a novel hemizygous deletion, c.6355 + 4_6355 + 5delAG, in intron 38 of the FLNA gene that the patient had inherited from his mother. cDNA studies showed that this variant results in the production of 3 aberrant FLNA transcripts, the most abundant of which results in retention of intron 38 of FLNA.

Conclusions

We report for the first time a case of early-onset SOD associated with a mutation in the FLNA gene. This finding broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum of the FLNAgene.