Analysis of clinical characteristics and NF1 gene variants in a child with Neurofibroma-Noonan syndrome
10.3760/cma.j.cn511374-20241112-00586
- VernacularTitle:神经纤维瘤病-努南综合征患儿1例的临床特征及 NF1基因变异分析
- Author:
Pingping WANG
1
;
Lianshu HAN
;
Suhong YANG
;
Jianmei ZHANG
;
Zhanli LIU
Author Information
1. 杭州市儿童医院内分泌科，杭州 310014
- Publication Type:Journal Article
- Keywords:
Neurofibromatoses;
Noonan syndrome;
NF1 gene;
Short stature;
Dysmorphic facial features;
Whole-exome sequencing;
Child
- From:
Chinese Journal of Medical Genetics
2025;42(4):419-423
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.
