We report the clinical and biochemical findings from a patient who presented with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal-dominant disorder characterized by optic atrophy, developmental delay and intellectual disability. In addition, the patient also displays hypotonia, stroke-like episodes, and complex IV deficiency of the mitochondrial respiratory chain. Whole-exome sequencing (WES) uncovered a novel heterozygous mutation in the NR2F1 gene (NM_005654:c.286A>G:p.Lys96Glu) that encodes for the COUP transcription factor 1 protein (COUP-TF1). Loss-of-function mutations in this protein have been associated with BBSOAS, and a luciferase reporter assay showed that this variant, in the zinc-finger DNA-binding domain (DBD) of COUP-TF1 protein, impairs its transcriptional activity. The additional features of this patient are more related with mitochondrial diseases that with BBSOAS, indicating a mitochondrial involvement. Finally, our data expand both the genetic and phenotypic spectrum associated with NR2F1 gene mutations.
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The authors thank the patient and her family for their contribution. This work was supported by the Spanish Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (ERDF) (grant PI10/00063 and PI14/00790 to FM-A). FJC-V was supported by fellowship from the Instituto de Investigación Hospital 12 de Octubre (i+12). PC-R was supported by fellowship from Comunidad de Madrid and European Social Fund (ESF) (PEJ16/MED/TL-1655). MER-G was supported by fellowship from ISCIII and ERDF (grant PI14/00790).
Conflict of interest
All the authors listed have approved the content of the manuscript. All authors declare that they have no conflict of interest.
Written informed consent was obtained from the patients’ parents, and the Ethic Committee of the Instituto de Investigación Hospital 12 de Octubre (i+12) approved the study.
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Martín-Hernández, E., Rodríguez-García, M.E., Chen, CA. et al. Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NR2F1 gene mutation. J Hum Genet 63, 525–528 (2018). https://doi.org/10.1038/s10038-017-0398-3
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