Claes Kathleen, Dahan Karin, Tejpar S, De Paepe Anne, Bonduelle Maryse, Abramowicz Marc, Verellen Christine, Franchimont Denis, Van Cutsem Eric, Kartheuser Alex
Belgian Polyposis Project, Familial Adenomatous Polyposis Association (FAPA), Brussels.
Acta Gastroenterol Belg. 2011 Sep;74(3):421-6.
FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of < 100 polyps and a later onset of colorectal cancer (CRC). (A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coli) gene, a tumour suppressor gene that controls beta-catenin turnover in the Wnt pathway. De novo occurrence is reported in 30-40% of the patients. Mutations are detected in 85% of classical FAP families, while only 20%-30% of AFAP cases will exhibit a germline APC mutation. MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations are inherited in an autosomal recessive way and account for 10%-20% of classical FAP cases without an APC mutation and for 30% of AFAP cases. Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical management. Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary. Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD).
家族性腺瘤性息肉病(FAP)的特征是在结肠和直肠中有100 - 1000个腺瘤性息肉,70%的患者伴有结肠外表现。 attenuated FAP(AFAP)是FAP的一种较轻形式,其特征是息肉少于100个,结直肠癌(CRC)发病较晚。FAP由APC(腺瘤性息肉病 coli)基因的常染色体显性遗传突变引起,APC是一种肿瘤抑制基因,控制Wnt通路中β-连环蛋白的周转。据报道,30 - 40%的患者为新发病例。85%的经典FAP家族可检测到突变,而只有20% - 30%的AFAP病例会出现种系APC突变。MUTYH是第二个与AFAP相关的基因,参与氧化应激损伤DNA的碱基切除修复。MUTYH突变以常染色体隐性方式遗传,占无APC突变的经典FAP病例的10% - 20%,占AFAP病例的30%。APC基因突变存在基因型 - 表型相关性,然而,文献中的矛盾之处提醒我们不要仅根据基因型来决定临床管理。一旦在先证者中确定了家族的特定APC突变,就可以从10至12岁开始对一级亲属进行预测性检测。对于AFAP,亲属在18岁及以上进行检测。关于开始基因检测的合适年龄的意见可能会有所不同。医生必须与育龄患者讨论产前检测问题。他们可以选择传统的产前诊断(羊膜穿刺术或绒毛取样)或植入前基因诊断(PGD)。
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