Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark.
J Hum Genet. 2023 Oct;68(10):721-724. doi: 10.1038/s10038-023-01174-w. Epub 2023 Jun 19.
Colorectal, hamartomatous juvenile polyps occur as part of different hereditary syndromes, including Juvenile polyposis syndrome and PTEN-hamartoma tumour syndrome. However, based on clinical manifestations alone, it is difficult to differentiate between the syndromes, and genetic analysis with an NGS-panel is often used to aid diagnostics. We report a 59-year-old male with colorectal juvenile polyps, who had been referred to genetic testing but had normal genetic analysis. He did not fulfil the clinical criteria of PTEN- hamartoma tumour syndrome, but the clinical criteria of Juvenile polyposis syndrome. With Whole Genome Sequencing we detected a novel intronic variant of unknown significance in PTEN (NC_000010.11:g.89687361 A > G(chr10, hg19), NM_000314.8:c.209 + 2047 A > G). RNA analysis classified the variant as likely pathogenic as it results in a pseudoexon inclusion introducing a frameshift and a premature stop codon. The patient was then diagnosed with PTEN-hamartoma Tumour syndrome. To our knowledge this is the first report of a variant resulting in pseudoexon inclusion in PTEN.
结直肠错构瘤性幼年性息肉作为不同遗传性综合征的一部分出现，包括幼年性息肉综合征和 PTEN 错构瘤肿瘤综合征。然而，仅基于临床表现，很难区分这些综合征，通常使用 NGS 面板进行遗传分析以辅助诊断。我们报告了一名 59 岁男性患有结直肠幼年性息肉，他曾接受基因检测，但基因分析正常。他不符合 PTEN 错构瘤肿瘤综合征的临床标准，但符合幼年性息肉综合征的临床标准。通过全基因组测序，我们在 PTEN 中检测到一个新的内含子变异，其意义未知（NC_000010.11：g.89687361 A>G（chr10，hg19），NM_000314.8：c.209+2047 A>G）。RNA 分析将该变异归类为可能具有致病性，因为它导致假外显子的包含，从而产生移码和过早终止密码子。随后该患者被诊断为 PTEN 错构瘤肿瘤综合征。据我们所知，这是首例报告导致 PTEN 假外显子包含的变异。
