A 35-year-old Filipino woman presented with epigastric pain and was found to have two large jejunal and ileal inflammatory fibroid polyps (IFPs) and dozens of subcentimeter small bowel submucosal nodules. Targeted exon sequencing of PDGFRA on the resected jejunum IFP identified a variant c.1664A>G that was subsequently confirmed in the germline. Family history was striking for three relatives with confirmed IFPs, including one with small bowel intussusception on five occasions. All relatives with IFPs were confirmed to have the same PDGFRA germline likely pathogenic variant, all were female, and all had IFPs by age 50 years that necessitated surgery. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This is the sixth reported family with a germline PDGFRA pathogenic variant and history of IFPs or gastrointestinal stromal tumor (GIST). This is the second report of the c.1664A>G likely pathogenic variant in a family that is unrelated to, and of different ethnic origin than, the first family. This second family exhibited a striking history of multiple IFPs without any reported GISTs, suggesting a possible genotype/phenotype association for this variant, and a possible female gender penetrance bias.

一名 35 岁的菲律宾女性因上腹痛就诊，发现有两个大的空肠和回肠炎性纤维瘤 (IFP) 和数十个亚厘米的小肠粘膜下结节。在切除的空肠 IFP 上对PDGFRA进行靶向外显子测序，鉴定了一个变异 c.1664A>G，随后在种系中得到证实。三名确诊 IFP 的亲属的家族史令人震惊，其中一名有五次小肠套叠。所有具有 IFP 的亲属都被确认具有相同的PDGFRA种系可能的致病性变异，都是女性，并且在 50 岁时都患有 IFP，需要手术。据报道，两名专性携带者具有相似的表型，而至少一名专性男性携带者没有报告 IFP 病史。这是第六个报告的具有种系PDGFRA致病性变异和 IFP 或胃肠道间质瘤 (GIST) 病史的家族。这是与第一个家族无关且种族不同的家族中 c.1664A>G 可能致病性变异的第二份报告。第二个家族表现出惊人的多个 IFP 历史，没有任何 GIST 报告，这表明该变体可能存在基因型/表型关联，以及可能存在女性性别外显偏倚。