Scholarlink

<p>Early-onset breast cancer in a woman prompted referral for genetic counseling, due to suspected hereditary cancer predisposition. After collecting a detailed personal and family medical history and providing comprehensive pre-test counseling, the patient consented to a multigene panel test for breast cancer susceptibility. Genetic analysis revealed a germline variant, c.662&#xa0;C &gt; T p.(Pro221Leu), in the <i>STK11</i> gene, initially classified as a variant of unknown significance (VUS). Given the possibility of Peutz-Jeghers syndrome (PJS), a thorough review of the patient’s extended family history was undertaken to identify clinical features consistent with the syndrome. The maternal grandmother’s lineage revealed a striking aggregation of malignancies, including eight cases of breast cancer (ages 34–73), one suspected gastric cancer before age 50, and five individuals with colorectal polyps. On the maternal grandfather’s side, nine breast cancer cases (ages 34–77), one childhood skin cancer, and one endometrial cancer at age 56 were described. Segregation studies in multiple relatives demonstrated co-segregation of the <i>STK11</i> variant with disease. This evidence supported the reclassification of the <i>STK11</i> c.622&#xa0;C &gt; T p.(Pro221Leu) variant as likely pathogenic. Consequently, carriers were enrolled in syndrome-specific surveillance protocols for PJS. This case underscores the essential role of comprehensive clinical and familial assessment, alongside segregation studies, in refining variant interpretation and enabling personalized, syndrome-specific management strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Reclassification of an uncertain STK11 germline variant as likely pathogenic: a family study

  • 期刊论文

  • 发表日期：

    2025年10月7日

查看全文
  • Lorena Moreno,
  • Miriam Cuatrecasas,
  • Elia Grau,
  • Míriam Potrony,
  • Josep Oriola,
  • Joan Anton Puig-Butillé,
  • Teresa Ocaña,
  • Teresa Ramón y Cajal,
  • Francesc Balaguer,
  • Sabela Carballal

摘要

Early-onset breast cancer in a woman prompted referral for genetic counseling, due to suspected hereditary cancer predisposition. After collecting a detailed personal and family medical history and providing comprehensive pre-test counseling, the patient consented to a multigene panel test for breast cancer susceptibility. Genetic analysis revealed a germline variant, c.662 C > T p.(Pro221Leu), in the STK11 gene, initially classified as a variant of unknown significance (VUS). Given the possibility of Peutz-Jeghers syndrome (PJS), a thorough review of the patient’s extended family history was undertaken to identify clinical features consistent with the syndrome. The maternal grandmother’s lineage revealed a striking aggregation of malignancies, including eight cases of breast cancer (ages 34–73), one suspected gastric cancer before age 50, and five individuals with colorectal polyps. On the maternal grandfather’s side, nine breast cancer cases (ages 34–77), one childhood skin cancer, and one endometrial cancer at age 56 were described. Segregation studies in multiple relatives demonstrated co-segregation of the STK11 variant with disease. This evidence supported the reclassification of the STK11 c.622 C > T p.(Pro221Leu) variant as likely pathogenic. Consequently, carriers were enrolled in syndrome-specific surveillance protocols for PJS. This case underscores the essential role of comprehensive clinical and familial assessment, alongside segregation studies, in refining variant interpretation and enabling personalized, syndrome-specific management strategies.