背景:Noonan综合征(NS)/Noonan综合征伴多个腹胀(NSML)通常以明显的面部特征为特征,身材矮小,心脏问题,和不同程度的发育延迟。然而,多达50%的被诊断为NS/NSML的个体由于表达变化和可能的不完全外显率而具有轻度影响的父母或亲戚。以及那些仅在诊断后才被确认患有NS的人在更明显受影响的索引病例中被确定。
方法:为了收集以前研究报告的代际数据,从2000年到2022年,搜索了包含PTPN11分子遗传学信息的电子期刊数据库。
结果:我们介绍了一个带有PTPN11变体的先证者案例(c.1492C>T/p。Arg498Trp)继承自无症状父亲,仅表现出轻度智力障碍,没有NS的经典症状。在我们的病例和报告的由PTPN11p.Arg498Trp变体引起的NS病例中,心脏异常(6/11),面部畸形(7/11),皮肤色素沉着(4/11),增长问题(4/11),并观察到感觉神经性听力损失(2/11)。患有PTPN11p.Arg498Trp变异的NS/NSML患者倾向于表现出相对较低的皮肤色素沉着频率,与携带任何其他突变PTPN11的患者相比,面部畸形和心脏异常以及轻度症状。
结论:由PTPN11p.Arg498Trp变体引起的父系遗传NS/NSML,包括我们的案子,可能表现出相对较低的异常特征和轻度症状的频率。这可能归因于潜在的基因-基因相互作用,基因-环境相互作用,传播父母的性别和表型,或影响临床表型的种族差异。
Noonan syndrome (NS)/Noonan syndrome with multiple lentigines (NSML) is commonly characterized by distinct facial features, a short stature, cardiac problems, and a developmental delay of variable degrees. However, as many as 50% of individuals diagnosed with NS/NSML have a mildly affected parent or relative due to variable expressivity and possibly incomplete penetrance of the disorder, and those who are recognized to have NS only after a diagnosis are established in a more obviously affected index
case.
In order to collect intergenerational data reported from previous studies, electronic journal databases containing information on the molecular genetics of PTPN11 were searched from 2000 to 2022.
We present a
case of a proband with a PTPN11 variant (c.1492C > T/p.Arg498Trp) inherited from an asymptomatic father, displaying only mild intellectual disability without classical symptoms of NS. Among our cases and the reported NS cases caused by the PTPN11 p.Arg498Trp variant, cardiac abnormalities (6/11), facial dysmorphism (7/11), skin pigmentation (4/11), growth problems (4/11), and sensorineural hearing loss (2/11) have been observed. NS/NSML patients with the PTPN11 p.Arg498Trp variant tend to exhibit relatively lower frequencies of skin pigmentation, facial dysmorphism and cardiac abnormalities and mild symptoms compared to those carrying any other mutated PTPN11.
Paternally inherited NS/NSML caused by a PTPN11 p.Arg498Trp variant, including our cases, may exhibit relatively lower frequencies of abnormal features and mild symptoms. This could be ascribed to potential gene-gene interactions, gene-environment interactions, the gender and phenotype of the transmitting parent, or ethnic differences that influence the clinical phenotype.