Ferreira Lize V, Souza Silvia A L, Montenegro Luciana R, Arnhold Ivo J P, Pasqualini Titania, Heinrich Juan Jorge, Keselman Ana Claudia, Mendonça Berenice B, Jorge Alexander A L
Laboratório de Hormônios e Genética Molecular, Disciplina de Endocrinologia do Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brasil.
Arq Bras Endocrinol Metabol. 2007 Apr;51(3):450-6. doi: 10.1590/s0004-27302007000300014.
Around 50% of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene.
To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation.
33 NS patients (23 males).
DNA was extracted from peripheral blood leukocytes, and all 15 PTPN11 exons were directly sequenced.
Nine different missense mutations, including the novel P491H, were found in 16 of 33 NS patients. The most frequently observed features in NS patients were posteriorly rotated ears with thick helix (85%), short stature (79%), webbed neck (77%) and cryptorchidism (60%) in boys. The mean height SDS was -2.7 +/- 1.2 and BMI SDS was -1 +/- 1.4. Patients with PTPN11 mutations presented a higher incidence of pulmonary stenosis than patients without mutations (38% vs. 6%, p< 0.05). Patients with and without mutations did not present differences regarding height SDS, BMI SDS, frequency of thorax deformity, facial characteristics, cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation test and IGF-1 or IGFBP-3 SDS.
We identified missense mutations in 48.5% of the NS patients. There was a positive correlation between the presence of PTPN11 mutations and pulmonary stenosis frequency in NS patients.
约50%的努南综合征（NS）患者存在PTPN11基因杂合突变。
评估NS患者中PTPN11基因突变频率，并进行表型-基因型相关性分析。
33例NS患者（23例男性）。
从外周血白细胞中提取DNA，对PTPN11基因的全部15个外显子进行直接测序。
在33例NS患者中的16例发现了9种不同的错义突变，包括新发现的P491H突变。NS患者最常见的特征是耳廓后旋伴耳轮增厚（85%）、身材矮小（79%）、蹼颈（77%）以及男孩隐睾（60%）。身高标准差分值（SDS）平均为-2.7±1.2，体重指数SDS为-1±1.4。与无PTPN11基因突变的患者相比，有该基因突变的患者肺动脉狭窄发生率更高（38%对6%，p<0.05）。有突变和无突变的患者在身高SDS、体重指数SDS、胸廓畸形频率、面部特征、隐睾、智力发育迟缓、学习障碍、刺激试验时生长激素峰值以及胰岛素样生长因子-1（IGF-1）或胰岛素样生长因子结合蛋白-3（IGFBP-3）SDS方面均无差异。
我们在48.5%的NS患者中鉴定出了错义突变。NS患者中PTPN11基因突变的存在与肺动脉狭窄频率之间存在正相关。
