Abstract
The genotype–phenotype correlation in BRAF variant in cardio-facio-cutaneous (CFC) syndrome is not clearly defined. Here we report a case with a severe clinical phenotype and a novel BRAF variant, p.Leu485del. The present case showed severe intellectual disability, impaired awareness, hyperekplexia, involuntary movements, early onset refractory seizures, and delayed myelination on brain magnetic resonance imaging as well as a polycystic and dysplastic kidney, which are previously unreported anomalies in CFC or RAS/mitogen-activated protein kinase syndromes related to BRAF variant. CFC syndrome, especially caused by BRAF variant, should be included in the differential diagnosis of patients with developmental and epileptic encephalopathies and hyperekplexia. Furthermore, we need to keep in mind that missense variants or the deletion of Leucine-485 may be associated with severe symptoms.
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SS-M and TM: study conceptualization, design, and manuscript preparation. KN, TN, and YA: functional analysis and interpretation of the data. SY-S, MA, YT, RS, TM, YO, WE, TI, NT: clinical evaluation. YT, AK, TN, and YA: gene analysis and interpretation of genetic analysis data. KH, YA, and SK: study concept, critical revision of the manuscript, and study supervision.
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Suzuki-Muromoto, S., Miyabayashi, T., Nagai, K. et al. Leucine-485 deletion variant of BRAF may exhibit the severe end of the clinical spectrum of CFC syndrome. J Hum Genet 64, 499–504 (2019). https://doi.org/10.1038/s10038-019-0579-3
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DOI: https://doi.org/10.1038/s10038-019-0579-3
