Davies D R, Armstrong J G, Thakker N, Horner K, Guy S P, Clancy T, Sloan P, Blair V, Dodd C, Warnes T W
Department of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom.
Am J Hum Genet. 1995 Nov;57(5):1151-8.
Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as "Gardner syndrome." Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dentoosseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5' of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3' of codon 1444, none of whom expressed CHRPE. Families with mutations 3' of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that the severity of some of the features of Gardner syndrome may correlate with genotype in FAP.
家族性腺瘤性息肉病（FAP）与多种肠外表现相关，包括骨瘤、表皮样囊肿和硬纤维瘤，这些通常被称为“加德纳综合征”。最近的研究表明，FAP的一些表型特征取决于APC基因内突变的位置。特别是，视网膜色素上皮先天性肥大（CHRPE）与APC基因型之间的相关性表明，受影响的家族可能分为不同的组。我们在一个地区性FAP家族队列中研究了加德纳综合征（GS）在牙科全景X线片（DPR）上的牙骨特征与APC基因型之间的关联。对来自36个家族的84名受影响个体进行了DPR检查，并通过加权评分系统对FAP的牙骨特征进行了量化。69%的受影响个体存在明显的DPR异常。在其中27个家族中鉴定出了APC基因突变，为了进行统计分析，将这些家族分为三组。第1组包括来自7个家族的18名受影响个体，其突变位于外显子9的5'端；这些家族（除一个家族外）不表达CHRPE。第2组包括来自16个家族的38名个体，其突变位于外显子9和密码子1444之间，所有这些个体均表达CHRPE。第3组包括来自4个家族的11名个体，其突变位于密码子1444的3'端，这些个体均不表达CHRPE。密码子1444的3'端发生突变的家族在DPR上的病变明显更多（P <.001），并且似乎硬纤维瘤的发病率更高。这些结果表明，加德纳综合征的某些特征的严重程度可能与FAP中的基因型相关。
