Shoji Yasuko, Hata Ayaha, Maeyama Takatoshi, Wada Tamaki, Hasegawa Yuiko, Nishi Eriko, Ida Shinobu, Etani Yuri, Niihori Tetsuya, Aoki Yoko, Okamoto Nobuhiko, Kawai Masanobu
Department of Gastroenterology and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan.
Department of Epidemiology and Health Policy, University of Toyama, Toyama, Japan.
Clin Pediatr Endocrinol. 2024;33(2):50-58. doi: 10.1297/cpe.2024-0005. Epub 2024 Feb 26.
Noonan syndrome (NS) is caused by pathogenic variants in genes encoding components of the RAS/MAPK pathway and presents with a number of symptoms, including characteristic facial features, congenital heart diseases, and short stature. Advances in genetic analyses have contributed to the identification of pathogenic genes in NS as well as genotype-phenotype relationships; however, updated evidence for the detection rate of pathogenic genes with the inclusion of newly identified genes is lacking in Japan. Accordingly, we examined the genetic background of 116 individuals clinically diagnosed with NS and the frequency of short stature. We also investigated genotype-phenotype relationships in the context of body mass index (BMI). Genetic testing revealed the responsible variants in 100 individuals (86%), where variants were the most prevalent (43%) and followed by (12%) and (9%). The frequency of short stature was the lowest in subjects possessing variants. No genotype-phenotype relationships in BMI were observed among the genotypes. In conclusion, this study provides evidence for the detection rate of pathogenic genes and genotype-phenotype relationships in Japanese patients with NS, which will be of clinical importance for accelerating our understanding of the genetic backgrounds of Japanese patients with NS.
努南综合征（NS）由编码RAS/MAPK通路成分的基因中的致病变异引起，表现出多种症状，包括特征性面部特征、先天性心脏病和身材矮小。基因分析的进展有助于确定NS中的致病基因以及基因型-表型关系；然而，在日本，缺乏纳入新发现基因后致病基因检测率的最新证据。因此，我们研究了116例临床诊断为NS的个体的遗传背景以及身材矮小的发生率。我们还在体重指数（BMI）的背景下研究了基因型-表型关系。基因检测在100例个体（86%）中发现了致病变异，其中 变异最为常见（43%），其次是 （12%）和 （9%）。身材矮小的发生率在携带 变异的受试者中最低。在各基因型之间未观察到BMI方面的基因型-表型关系。总之，本研究为日本NS患者致病基因的检测率和基因型-表型关系提供了证据，这对于加快我们对日本NS患者遗传背景的理解具有临床重要性。
