Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NR2F1 gene mutation

作者：Martin Hernandez Elena; Elena Rodriguez Garcia Maria; Chen Chun An; Javier Cotrina Vinagre Francisco; Carnicero Rodriguez Patricia; Bellusci Marcello; Schaaf Christian P; Martinez Azorin Francisco^*

来源：Journal of Human Genetics, 2018, 63(4): 525-528.

DOI：10.1038/s10038-017-0398-3

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-offunction 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.

• 出版日期2018-4