Sarkozy Anna, Obregon Maria Gabriela, Conti Emanuela, Esposito Giorgia, Mingarelli Rita, Pizzuti Antonio, Dallapiccola Bruno
CSS Hospital, IRCCS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
Eur J Hum Genet. 2004 Dec;12(12):1069-72. doi: 10.1038/sj.ejhg.5201290.
Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders.
努南综合征（NS）和多发性雀斑样痣/豹皮综合征（LS）已被证明与不同的PTPN11突变相关。努南样/多发性巨细胞病变综合征（NLS）是一种罕见疾病，其特征为身材矮小、面部畸形、先天性心脏缺陷（CHD）和中枢性巨细胞病变。在一个NLS家族和两名散发性患者中曾报道过PTPN11基因突变。在此，我们报告一名具有复杂表型的患者，其表型多年来从出生时的NS逐渐发展为LS和NLS。PTPN11基因分析揭示了外显子12中的一个新的错义突变（Ala461Thr），影响了SHP2活性位点的共有序列。这一观察结果将NS、LS和NLS合并为一种独特的基因缺陷，拓宽了PTPN11相关疾病的临床和分子谱。
