SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome
SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome
复制标题
SOS1 是第二常见的 Noonan 基因，但在心脏-面部-皮肤综合征中不起主要作用
作者：
M. Zenker;D. Horn;D. Wieczorek;J. Allanson;S. Pauli;I. van der Burgt;H. Doerr;H. Gaspar;M. Hofbeck;G. Gillessen‐Kaesbach;A. Koch;P. Meinecke;S. Mundlos;Anja Nowka;A. Rauch;Silke Reif;C. von Schnakenburg;H. Seidel;L. Wehner;C. Zweier;Susanne Bauhuber;Verena Matejas;C. Kratz;Christoph Thomas;K. Kutsche
背景：编码 Ras-MAPK 信号级联蛋白的各种基因的杂合功能获得突变已被确定为努南综合征 (NS) 和心脏面皮综合征 (CFCS) 的遗传基础。 SOS1（编码 Ras 鸟嘌呤核苷酸交换因子的基因）的突变是 NS 患者中的最新发现，但尚未在 CFCS 患者中研究该基因。方法和结果：我们在一大群患有 NS-CFCS 谱系疾病的患者中研究了 SOS1，这些患者之前的 PTPN11、KRAS、BRAF、MEK1 和 MEK2 突变检测呈阴性。在 28% 的 NS 患者中发现了 SOS1 错义突变。相比之下，没有发现被归类为患有 CFCS 的患者携带该基因的致病序列变化。结论：我们已经确认SOS1是NS的第二个主要基因。携带该基因突变的患者具有独特的表型，经常出现外胚层异常，例如毛周角化症和卷发。然而，与 SOS1 突变相关的临床表现与 CFCS 不同。这些发现证实，尽管 NS 和 CFCS 是由属于同一途径的分子的功能获得突变引起的，但它们在基因型上几乎没有重叠。
Background: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. Methods and results: We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. Conclusion: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.
影响因子：
9.8
作者：
Tartaglia, M;Kalidas, K;Gelb, BD
通讯作者：
Gelb, BD