Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Respiratory Infection and Antimicrobial Resistance Group, Infectious Diseases Area, BioDonostia; Microbiology Department, Osakidetza Basque Health Service, Donostialdea Integrated Health Organization, San Sebastian, Spain.
Orphanet J Rare Dis. 2022 Feb 28;17(1):85. doi: 10.1186/s13023-021-02079-7.
The limited knowledge about the PTEN hamartoma tumor syndrome (PHTS) makes its diagnosis a challenging task. We aimed to define the clinical and genetic characteristics of this syndrome in the Spanish population and to identify new genes potentially associated with the disease.
We reviewed the clinical data collected through a specific questionnaire in a series of 145 Spanish patients with a phenotypic features compatible with PHTS and performed molecular characterization through several approaches including next generation sequencing and whole exome sequencing (WES). Macrocephaly, mucocutaneous lesions, gastrointestinal polyposis and obesity are prevalent phenotypic features in PHTS and help predict the presence of a PTEN germline variant in our population. We also find that PHTS patients are at risk to develop cancer in childhood or adolescence. Furthermore, we observe a high frequency of variants in exon 1 of PTEN, which are associated with renal cancer and overexpression of KLLN and PTEN. Moreover, WES revealed variants in genes like NEDD4 that merit further research.
This study expands previously reported findings in other PHTS population studies and makes new contributions regarding clinical and molecular aspects of PHTS, which are useful for translation to the clinic and for new research lines.
PTEN 错构瘤肿瘤综合征（PHTS）的知识有限，使得其诊断成为一项具有挑战性的任务。我们旨在定义该综合征在西班牙人群中的临床和遗传特征，并确定与该疾病相关的新基因。
我们通过专门的问卷回顾了一系列 145 名与 PHTS 表型特征相符的西班牙患者的临床数据，并通过包括下一代测序和全外显子组测序（WES）在内的多种方法进行了分子特征分析。大头畸形、黏膜皮肤病变、胃肠道息肉病和肥胖症是 PHTS 中常见的表型特征，有助于预测我们人群中是否存在 PTEN 种系变异。我们还发现 PHTS 患者在儿童或青少年时期有患癌症的风险。此外，我们观察到 PTEN 外显子 1 中的变异频率很高，这些变异与肾癌和 KLLN 和 PTEN 的过表达有关。此外，WES 还揭示了 NEDD4 等基因的变异，值得进一步研究。
本研究扩展了先前在其他 PHTS 人群研究中报告的发现，并对 PHTS 的临床和分子方面做出了新的贡献，这对于转化为临床实践和新的研究方向都很有用。
