NF1 Genetic Testing and Structural Analysis in Pediatric Patients with Neurofibromatosis Presenting Predominantly with Café-au-lait Macules
WANG Yuhan
CHEN Jianyou
LIU Xiaoyan
WANG Jianhua
ZHANG Gaolei
Abstract：Objective To identify NF1 gene variants and evaluate their potential functional impact in children whose principal clinical feature is multiple café-au-lait macules.Methods We retrospectively reviewed 93 children seen at the Capital Center for Children's Health,Capital Medical University from January 2019 to October 2023 for multiple café-au-lait macules(>6 lesions,each>5 mm)and with a high clinical suspicion of neurofibromatosis type 1(NF1).Probands underwent next-generation sequencing;candidate variants were confirmed by Sanger sequencing in family members where available.To assess potential structural consequences of missense substitutions,we examined protein three-dimensional models from the RCSB Protein Data Bank.Results Pathogenic or likely pathogenic NF1 variants were detected in 43 of 93 families(detection rate 46.24%).Eight of the identified variant sites were novel and have not been previously reported.The variant spectrum was dominated by de novo truncating mutations(nonsense and frameshift),consistent with loss-of-function mechanisms.Conclusion Among children presenting mainly with multiple café-au-lait macules,NF1 mutations are frequently de novo and are predominantly truncating variants.The identification of eight novel NF1 mutation sites expands the mutational spectrum and will aid clinical diagnosis and genetic testing for NF1.
Keywords：neurofibromatosiscafé-au-lait maculesNF1 genegene mutation
Publication Date：2026-02-10
Online Publishing Date：2026-03-17(First online date of this platform, not the publication date of the document)
Pages：6( 12-17 )