Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband’s children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.

中文翻译：

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家族性幼虫息肉综合征与BMPR1A基因从头种系错义变异：病例报告

少年息肉综合征（JPS）是一种罕见的常染色体显性遗传性疾病，其特征是胃肠道中出现了多种不同的少年息肉，从而增加了结直肠癌的风险。已经确定了两个基因SMAD4和BMPR1A的种系突变导致JPS。在这里，我们报告了一个幼年息肉病家庭的外显子3 BMPR1A基因中的种系杂合错义变体（c.299G> A）。人口数据库中没有此变体，与亲本测序相比，从头得出结论。先证者子女的进一步测序证实了该变异体与疾病的隔离，而基于在线预测工具也预测该变异体具有破坏作用。因此，根据美国医学遗传学和基因组学（ACMG）指南，该变体被归类为可能的致病菌。生殖细胞遗传测试显示，在一个年轻的息肉病家庭中，BMPR1A基因有一个新的生殖系错义变体。病原体变异的鉴定有助于对高危家庭成员的癌症风险管理，建议对突变携带者进行内窥镜监测。