Table of Contents

HK J Paediatr (New Series)
Vol 11. No. 4, 2006

HK J Paediatr (New Series) 2006;11:290-296

Original Article

A Clinical and Molecular Study of 51 Chinese Families with Noonan Syndrome
51 個中國 Noonan 綜合徵家系的臨床和分子學分析

DKH Chan, IFM Lo, ACF Lam, TMF Tong, DHC Chan, STS Lam


Objective: To study the clinical spectrum of Chinese Noonan syndrome and perform the mutational analysis of Protein-Tyrosine Phosphatase, Non-receptor 11 (PTPN11) among them. Method: Fifty-one unrelated Noonan patients and their parents were enrolled according to a modified inclusion scoring system. In addition, Noonan-like syndromes including 2 cases of Cardio-faciocutaneous (CFC) syndrome and 1 Costello patient were tested for PTPN11 mutation. Results: Thirty-nine sporadic and 12 familial cases of Noonan syndrome were ascertained clinically. Of these familial cases, maternal versus paternal transmission occurred at a ratio of 11:1. Thirty-two index cases and 9 familial cases were found to have mutations in PTPN11 gene. Heterozygous missense mutation of PTPN11 and recurrent mutation N308D (c.922A>G) constituted 62.7% and 28.1% respectively. Five novel mutations were reported. Genotype-phenotype correlation revealed that exon 3 and 13 mutations were significantly associated with typical faces (p<0.044). Exon 3/c.181G>A mutation was noted to present more prominent ectodermal features like sparse hair and eyebrows. No mutation of PTPN11 gene was identified in CFC and Costello patients. Conclusion: These results demonstrate the role of PTPN11 gene in the expression of the phenotype. However, other gene(s) may also be involved in the pathogenesis of Noonan phenotype. The mutational screening of PTPN11 is recommended to ascertain those affected parents with less obvious phenotype and Noonan syndrome associated with atypical features.

目的:研究中國 Noonan 綜合徵的臨床疾病譜並分析 PTPN11 基因在這些家系中的基因突變。方法:根據改良的選取計分系統選取 51 個無相關性的 Noonan 綜合徵患者和其父母。另外,還分析了類 Noonan 綜合徵的 PTPN11 基因突變,包括 2 例心臟─臉─皮膚(CFC)症候群和 1 例 Costello 患者。結果:臨床確診 39 例散發和 12例家族性 Noonan 綜合徵患者。在家族性患者中,母系遺傳和父系遺傳的比率是 11:1。發現 32 例先證者和 9 例家族性患者存在 PTPN11 基因突變。PTPN11 基因的雜合錯義突變佔 62.7%,N308D(c.922A>G)基因的頻發突變佔 28.1%。發現 5 個新的突變。基因型─表型相關性分析發現外顯子 3 和 13 突變與典型的面部表現呈顯著性相關(p<0.044)。外顯子 3/c.181G>A 突變會表現為更多的毛髮特徵如頭髮和眉毛稀疏,徵狀明顯。在 CFC 和 Costello患者中未發現 PTPN11 基因突變。結論:研究結果表明 PTPN11 基因在 Noonan 綜合徵的表型表達中起作用。但是,其他基因也可能參與了表型的發病。 PTPN11 基因突變檢測可用於確診表型不明顯的患者父母和表現不典型的 Noonan 綜合徵患者。

Keyword : Diagnostic scoring system; Genotype-Phenotype correlation; Missense mutation; Noonan syndrome; PTPN11 gene

關鍵詞:診斷計分系統、基因型─表型相關性、錯義突變、 Noonan 綜合徵、PTPN11 基因


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