Affiliation:
1. Department of Burns and Plastic Surgery at The Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Regional Medical Center for Children Hangzhou Zhejiang China
2. The Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Regional Medical Center for Children Hangzhou Zhejiang China
Abstract
Abstract
Background
Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined.
Aim
To determine the correlation of variants allele load and different phenotypes of CMN.
Methods
A panel of genes in the Ras/Raf/MAPK signalling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes, including anatomical localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, colour variation and hypertrichosis, were analysed.
Results
In addition to the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS (p.G13R and p.M72fs), BRAF (p.D22N) and MAP2K1 (p.I107fs, p.F209fs, p.Q354H and p.G91_L92insHDQARRLVGDLEHHKPSG). Furthermore, a higher allele load of NRAS p.Q61R/K was found in the trunk and limbs of CMN. It was also found in CMN with larger size, higher colour variation and more significant hypertrichosis, surface rugosity and asymmetry.
Conclusion
We discovered more genetic variants of NRAS, BRAF and MAP2K1 and established a correlation between the allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitate a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics used in clinical practice.
Funder
National Natural Science Foundation of China
Zhejiang Province Health Innovative Talents Project
Publisher
Oxford University Press (OUP)
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