LaFemina Jennifer, Roberts Penelope A, Hung Yin P, Gusella James F, Sahani Dushyant, Fernández-del Castillo Carlos, Warshaw Andrew L, Thayer Sarah P
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Pancreatology. 2009;9(3):273-9. doi: 10.1159/000201553. Epub 2009 Apr 29.
BACKGROUND/AIMS: Hereditary pancreatic cancer comprises about 10% of pancreatic cancer cases. Multiple causative mutations have been identified. Here we describe a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis and pancreatic cancer resulting from an uncharacterized mutation.
Family members completed evaluations to determine signs of mutation status. Select patients were screened for mutations associated with hereditary pancreatic diseases.
In generation II, 12 siblings exhibit 6 cases of pancreatitis, 3 pancreatic cancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis of enrolled members is 32.5 years; average age at pancreatic cancer diagnosis is 59 years. There is no association with known cancer syndromes. Those affected generally present with mild epigastric pain, and CT scans demonstrate characteristic fatty infiltration of the pancreatic body and tail with sparing of the head and neck. Full sequence analysis of genes associated with hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms.
Based upon pedigree evaluation and preliminary DNA analysis, we believe that the family members with P/PC carry a novel genetic mutation resulting in hereditary pancreatitis. This mutation is autosomal dominant, expressed with high penetrance, and is part of a unique hereditary syndrome that significantly increases pancreatic cancer risk.
背景/目的：遗传性胰腺癌约占胰腺癌病例的10%。已鉴定出多种致病突变。在此，我们描述了一个胰腺炎/胰腺癌（P/PC）家族，该家族表现出由一种未鉴定的突变导致的胰腺炎和胰腺癌。
家族成员完成评估以确定突变状态的体征。对选定患者进行与遗传性胰腺疾病相关的突变筛查。
在第二代中，12名兄弟姐妹中有6例胰腺炎、3例胰腺癌和2例肯定携带者状态。登记成员胰腺炎诊断的平均年龄为32.5岁；胰腺癌诊断的平均年龄为59岁。与已知癌症综合征无关。患者通常表现为轻度上腹部疼痛，CT扫描显示胰体和胰尾有特征性脂肪浸润，而胰头和胰颈未受累。对与遗传性胰腺疾病相关基因的全序列分析未显示已知突变或多态性。
基于系谱评估和初步DNA分析，我们认为患有P/PC的家族成员携带一种导致遗传性胰腺炎的新基因突变。这种突变是常染色体显性遗传，具有高外显率，并且是一种独特的遗传综合征的一部分，该综合征显著增加胰腺癌风险。
