GeneDx, 207 Perry Parkway, Gaithersburg, MD, 20877, USA.
My Gene Team, Miami, FL, USA.
Fam Cancer. 2019 Apr;18(2):203-209. doi: 10.1007/s10689-018-00116-2.
Biallelic pathogenic variants (PVs) in MUTYH cause MUTYH-Associated Polyposis (MAP), which displays phenotypic overlap with other hereditary colorectal cancer (CRC) syndromes including Familial Adenomatous Polyposis (FAP) and Lynch syndrome. We report the phenotypic spectrum of MAP in the context of multi-gene hereditary cancer panel testing. Genetic testing results and clinical histories were reviewed for individuals with biallelic MUTYH PVs detected by panel testing at a single commercial molecular diagnostic laboratory. Biallelic MUTYH PVs were identified in 82 individuals (representing 0.2% of tested individuals) with most (75/82; 91.5%) reporting a personal history of CRC and/or polyps. Ten percent (6/61) of individuals reporting polyp number reported fewer than 10 polyps and therefore did not meet current MAP testing criteria. Extracolonic cancers (21/82; 25.6%), multiple primaries (19/82; 23.2%), Lynch-like (17/82; 20.7%) and FAP-like phenotypes (16/82; 19.5%) were observed, including individuals with mismatch repair-deficient tumors (3/82; 3.7%), sebaceous neoplasms (2/82; 2.4%), or congenital hypertrophy of the retinal pigment epithelium (CHRPE) (2/82; 2.4%). We report what is to our knowledge the first cohort of individuals with MAP identified by panel testing. The phenotypic spectrum of MAP observed in this cohort aligns with the published literature. In addition to standard indications for MUTYH testing, our data provide evidence to support consideration of MAP in the differential diagnosis for some individuals with fewer than 10 polyps, depending on other personal and/or family history, as well as for individuals suspected to have Lynch syndrome or FAP.
双等位致病性变异（PVs）在 MUTYH 中引起 MUTYH 相关息肉病（MAP），其表型与其他遗传性结直肠癌（CRC）综合征重叠，包括家族性腺瘤性息肉病（FAP）和林奇综合征。我们在多基因遗传性癌症面板检测的背景下报告 MAP 的表型谱。在一家商业分子诊断实验室进行的面板检测中，检测到双等位 MUTYH PVs 的个体的基因检测结果和临床病史进行了回顾。在 82 名个体中鉴定出双等位 MUTYH PVs（占检测个体的 0.2%），其中大多数（75/82；91.5%）报告有 CRC 和/或息肉的个人病史。报告息肉数量的个体中有 10%（6/61）报告少于 10 个息肉，因此不符合当前的 MAP 检测标准。观察到 21/82（25.6%）的个体发生了结肠外癌症、19/82（23.2%）的个体发生了多个原发性肿瘤、17/82（20.7%）的个体发生了林奇样表型和 16/82（19.5%）的个体发生了 FAP 样表型，包括 3/82（3.7%）的错配修复缺陷型肿瘤、2/82（2.4%）的皮脂腺肿瘤或 2/82（2.4%）的先天性视网膜色素上皮肥厚（CHRPE）。我们报告了据我们所知，通过面板检测首次确定的 MAP 个体队列。在本队列中观察到的 MAP 表型谱与已发表的文献一致。除了 MUTYH 检测的标准指征外，我们的数据还提供了证据，支持在其他个人和/或家族史的基础上，在某些个体的息肉少于 10 个时，考虑 MAP 的鉴别诊断，以及在怀疑患有林奇综合征或 FAP 时，考虑 MAP 的鉴别诊断。
