Traboulsi E I, Apostolides J, Giardiello F M, Krush A J, Booker S V, Hamilton S R, Hussels I E
Johns Hopkins Center for Hereditary Eye Diseases, Wilmer Ophthalmological Institute, Baltimore, MD, USA.
Ophthalmic Genet. 1996 Dec;17(4):167-74. doi: 10.3109/13816819609057890.
Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21. The extracolonic manifestations of FAP include pigmented ocular fundus lesions (POFLS), cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. POFLS are present at birth in about 80% of patients with FAP and are excellent clinical congenital markers for the disease. We studied the distribution of POFLS by number and APC mutation in families of the Johns Hopkins Polyposis Registry.
Of the 51 families with FAP, 42 (82%) had an identifiable APC mutation. We correlated the presence/absence and distribution by number of POFLS with the type and location of the mutation in the APC gene in 21 families where an ocular examination had been performed in at least one affected member, and where a systematic search for mutations in the APC gene had been undertaken. Families were considered POFL-positive if the average number of lesions per patient was three or more, or if at least one family member had three or more lesions.
Fifteen of the 21 families (71.4%) were POFL-positive. Mutations of the APC gene were detected in 15 of the 21 families. Of these, 12 (80%) were POFL-positive. Families with mutations at condons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations at condons 541, 625, 1055, 1059, 1061, 1230, 1309, 1465, and 1546 (exons 12-15) were POFL-positive. One patient with a mutation at codon 2621 (exon 15) had no POFLS.
Mutations in exons 1-8 and the distal portion of exon 15 of the APC gene are associated with a POFL-negative phenotype, while those in exons 10 to the proximal portion of exon I5 are generally associated with a POFL-positive
家族性腺瘤性息肉病（FAP）由5号染色体长臂21区（5q21）的腺瘤性息肉病基因（APC）的种系突变引起。FAP的结肠外表现包括色素性眼底病变（POFLS）、皮肤囊肿、骨瘤、隐匿性不透射线的颌骨病变、牙瘤、硬纤维瘤和结肠外癌症。约80%的FAP患者出生时即有POFLS，是该疾病良好的临床先天性标志物。我们研究了约翰霍普金斯息肉病登记处家族中POFLS的数量分布及APC突变情况。
在51个FAP家族中，42个（82%）有可识别的APC突变。在至少一名受累成员进行了眼部检查且对APC基因进行了系统突变检测的21个家族中，我们将POFLS的有无及数量分布与APC基因的突变类型和位置进行了关联。如果每位患者的病变平均数量为三个或更多，或者至少有一名家庭成员有三个或更多病变，则该家族被视为POFL阳性。
21个家族中有15个（71.4%）为POFL阳性。21个家族中检测到15个APC基因突变。其中，12个（80%）为POFL阳性。密码子215（第5外显子）和302（第8外显子）发生突变的家族为POFL阴性。密码子541、625、1055、1059、1061、1230、1309、1465和1546（第12 - 15外显子）发生突变的家族为POFL阳性。一名密码子2621（第15外显子）发生突变的患者没有POFLS。
APC基因第1 - 8外显子和第I5外显子远端部分的突变与POFL阴性表型相关，而第10外显子至第I5外显子近端部分的突变通常与POFL阳性相关。
