English

BRAF

Gene product: B-Raf Proto-Oncogene, Serine/Threonine Kinase.

Protein function: It is a member of the RAF serine/threonine protein kinase family and a key component of the RAS-MAPK signaling pathway (Figure 1). It can phosphorylate MAP2K1 and plays an important role in cell proliferation, differentiation, survival, migration and metabolism [1-2].

Phenotype: 1. Cardiofaciocutaneous syndrome (AD) (some may have developmental delay and epileptic seizures, and some may present with Infantile Epileptic Spasms Syndrome) [3-4]; 2. LEOPARD syndrome (AD) [5]; 3. Noonan syndrome (AD) [6].

Mutation database: ClinVar.

Clinical research: PubMed (PMID: 37827855 (Am J Med Genet A. 2024))

Medication reminder: The choice of medication is mainly based on different Epilepsy Syndromes. Some of them may present as refractory epileptic seizures. Literature reports that some children have a good response to oxcarbazepine [10]. There are also reports on the use of BRAF inhibitors and MEK inhibitors to treat epilepsy caused by this gene mutation [7-8]. In addition, if imaging clearly indicates structural lesions (such as cortical dysplasia, low-grade glioma) and the electro-clinical-imaging matches, surgery may also be an option for drug-resistant epilepsy caused by this gene mutation [9] (personal opinion, for reference only).

 

Figure 1

BRAF示意图

 

 

References:

  1. The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway. Endocr Rev. 2018 Oct 1;39(5):676-700.
  2. Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy. J Clin Invest. 2018 Apr 2;128(4):1496-1508.
  3. Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome. Clin Genet. 2008 Jan;73(1):62-70.
  4. Infantile epileptic spasms syndrome in children with cardiofaciocutanous syndrome: Clinical presentation and associations with genotype. Am J Med Genet C Semin Med Genet. 2022 Dec;190(4):501-509.
  5. Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence. Eur J Med Genet. 2009 Sep-Oct;52(5):337-40.
  6. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009 Apr;30(4):695-702.
  7. Seizure control in tumor-associated epilepsy secondary to BRAF inhibition. Pediatr Blood Cancer. 2023 Apr;70(4):e30073.
  8. Treatment of Refractory Epilepsy With MEK Inhibitor in Patients With RASopathy. Pediatr Neurol. 2023 Nov:148:148-151.
  9. BRAF V600E Mutation in Ganglioglioma: Impact on Epileptogenicity and Implications for Surgical Strategy. Eur J Neurol. 2025 Apr;32(4):e70136.
  10. Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti-seizure medication. Am J Med Genet A. 2024 Feb;194(2):301-310.
 
  • 达哥的闲言碎语