关键词: RAS通路病, BRAF(p.Asp638Glu), 临床表型

Abstract:

Objective To investigate the association between BRAF (v-raf murine sarcoma viral oncogene homolog B) gene variant sites and the clinical phenotypes of RASopathies, and to improve understanding, diagnosis, and management of this disease. Methods A retrospective analysis was performed of the clinical data of a child with a BRAF (p.Asp638Glu) gene variant who was treated at Maternity and Child Health Care of Guangxi Zhuang Autonomous Region. CNKI, Wanfang Data, Google Scholar, and PubMed were searched to collect reported cases with the same variant site, and their clinical phenotypes were compared and analyzed. Results The child in this case mainly presented with feeding difficulties after birth, growth and developmental delay, diarrhea, recurrent respiratory tract infections, and febrile seizures. Genetic testing revealed a heterozygous BRAF c.1914T>G (p.Asp638Glu) variant. The literature search identified 13 reported cases with the BRAF (p.Asp638Glu) variant, and phenotype comparison was conducted across 14 cases in total. The following phenotypes were confirmed: developmental delay, 13/14; abnormal brain structures on cranlar MRI, 11/14; epilepsy, 9/14; feeding difficulties, 9/14; short stature, 9/14; distinctive facial features, 8/14; skin and hair abnormalities, 8/14; and cardiac abnormalities, 3/14.Conclusion RASopathies associated with the BRAF (p.Asp638Glu) variant are characterized by multisystem involvement, with frequent impairment of the nervous, digestive, and skin systems. The phenotype shows overlap and heterogeneity, and no clear genotype-phenotype correlation has yet been identified. Early genetic testing is recommended for clinically suspected cases to confirm the diagnosis.

Key words: RASopathies, BRAF (p.Asp638Glu), clinical phenotype