Familial juvenile polyposis syndrome with a de novo germline missense variant in BMPR1A gene: a case report
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CASE REPORT
Open Access
Familial juvenile polyposis syndrome with a de novo germline missense variant in BMPR1A gene: a case report Qing Liu, Mengling Liu, Tianshu Liu and Yiyi Yu*
Abstract Background: 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. Case presentation: 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. Conclusions: 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. Keywords: Juvenile polyposis syndrome, BMPR1A gene, De novo germline variant, Missense variant
Background 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 [1, 2]. Clinically, JPS is defined by the presence of more than five juvenile polyps in the colorectum, and/or juvenile polyps outside the colon, and/or any number of juvenile polyps with a family history of juvenile polyposis [3]. Histologically, these polyps are characterized by an abundance of edematous lamina propria with mucin-filled cystic dilations and inflammatory infiltrate [4]. Germline mutations in * Correspondence: [email protected] Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China
two genes, SMAD4 and BMPR1A, have been identified to cause JPS [5]. Both genes are members of the transforming growth factor beta (TGF-β) superfamily, and pathogenic mutations in the coding region of each gene have been found in ~ 20% of JPS patients, respectively [6]. Here we report a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis.
Case presentation The 35-year-old male proband was first presented with rectal bleeding for 2 months in September 2015 (Fig. 1). Colonoscopy was then conducted and revealed dozens of pedunculated polyps of different sizes (range of 5–30 mm), distributed along the entire length of the colon. The histological analysis showed juvenile and adenomatous polyp wit
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