Sznajer Yves, Keren Boris, Baumann Clarisse, Pereira Sabrina, Alberti Corinne, Elion Jacques, Cavé Hélène, Verloes Alain
Department of Medical Genetics, AP-HP Robert Debré University Hospital, Paris, France.
Pediatrics. 2007 Jun;119(6):e1325-31. doi: 10.1542/peds.2006-0211. Epub 2007 May 21.
Noonan syndrome is a clinically homogeneous but genetically heterogeneous condition. Type 1 Noonan syndrome is defined by the presence of a mutation in the PTPN11 gene, which is found in approximately 40% of the cases. Phenotype descriptions and cardiac defects from cohorts with Noonan syndrome were delineated in the "pregenomic era." We report the heart defects and links to gene dysfunction in cardiac development in a large cohort of patients with type 1 Noonan syndrome.
This was a retrospective, multicenter study based on clinical history, pictures, and medical and cardiologic workup over time. Data were collected by referral geneticists. Mutation screening was performed by direct sequencing of exons 2, 3, 4, 7, 8, 12, and 13 and their intron-exon boundaries, which harbor 98% of identified mutations the PTPN11 gene.
A PTPN11 gene mutation was identified in 104 (38.25%) of 274 patients with Noonan syndrome. Heart defect was present in 85%. The most prevalent congenital heart defects were pulmonary valve stenosis (60%), atrial septal defect, ostium secundum type (25%), and stenosis of the peripheral pulmonary arteries (in at least 15%). Pulmonary valve stenosis and atrial septal defect, ostium secundum type, were significantly associated with the identification of a mutation in the PTPN11 gene. Ventricular septal defect and most left-sided heart defects showed a trend toward overrepresentation in the group without a mutation.
We compared our data with previous series and integrated the comprehension of molecular PTPN11 gene dysfunction in heart development.
努南综合征是一种临床特征相同但基因异质性的疾病。1型努南综合征由PTPN11基因突变所定义，约40%的病例存在该突变。在“基因组时代之前”，已有关于努南综合征队列的表型描述和心脏缺陷的报道。我们报告了一大群1型努南综合征患者的心脏缺陷及其与心脏发育中基因功能障碍的关联。
这是一项基于临床病史、图片以及随时间进行的医学和心脏病学检查的回顾性多中心研究。数据由转诊的遗传学家收集。通过对第2、3、4、7、8、12和13外显子及其内含子-外显子边界进行直接测序来进行突变筛查，这些区域包含了已鉴定的PTPN11基因98%的突变。
在274例努南综合征患者中，104例（38.25%）检测到PTPN11基因突变。85%的患者存在心脏缺陷。最常见的先天性心脏缺陷是肺动脉瓣狭窄（60%）、继发孔型房间隔缺损（25%）和外周肺动脉狭窄（至少15%）。肺动脉瓣狭窄和继发孔型房间隔缺损与PTPN11基因突变的检出显著相关。室间隔缺损和大多数左侧心脏缺陷在未发生突变的组中呈现出过度出现的趋势。
我们将我们的数据与先前的系列研究进行了比较，并整合了对心脏发育中PTPN11基因分子功能障碍的理解。
