Ferreira Lize V, Souza Silvia C A L, Montenegro Luciana R, Malaquias Alexsandra C, Arnhold Ivo J P, Mendonca Berenice B, Jorge Alexander A L
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
Clin Endocrinol (Oxf). 2008 Sep;69(3):426-31. doi: 10.1111/j.1365-2265.2008.03234.x. Epub 2008 Mar 10.
Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS.
To evaluate the presence of mutations in PTPN11 in ISS children who presented NS-related signs and in well-characterized NS patients.
We studied 50 ISS children who presented at least two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty-nine NS patients diagnosed by the criteria of van der Burgt et al. were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing.
No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations.
Considering that no mutations were found in the present cohort with NS-related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.
蛋白酪氨酸磷酸酶非受体型11（PTPN11）基因突变是努南综合征（NS）的主要病因。特发性身材矮小（ISS）儿童中经常出现一些NS特征。这些儿童可能代表NS临床谱系中较轻的一端，PTPN11是参与ISS发病机制的一个很好的候选基因。
评估出现NS相关体征的ISS儿童以及特征明确的NS患者中PTPN11基因突变的情况。
我们研究了50例出现至少两种NS相关体征但不符合NS诊断标准的ISS儿童。采用范德伯格特等人的标准诊断的49例NS患者用于评估这些标准在选择PTPN11突变筛查患者方面的适用性。通过聚合酶链反应（PCR）扩增PTPN11的编码区，随后进行直接测序。
ISS儿童的PTPN11基因编码区未发现突变或多态性。49例NS患者中有19例（39%）出现PTPN11突变。没有单一特征能够使我们区分有或没有PTPN11突变的NS患者。
鉴于在本队列中有NS相关体征的患者中未发现突变，在未经选择的ISS儿童中发现突变的可能性不大。范德伯格特等人的标准在实现NS诊断和选择分子研究患者方面是适用的。PTPN11基因突变通常参与NS的发病机制，但不是ISS的常见病因。
