Screening by Genomic Linkage Studies and Mutation Analysis of Hereditary Adenomatous Polyposis Coli: Usefulness for Clinical Practice

Overview

Journal World J Surg

Publisher Wiley

Specialty General Surgery

Date 1996 Jun 1

PMID 8661634

Citations 1

Authors

J Karner-Hanusch

B Wolf

M Zehetmayer

F Wrba

E Roth

C Mannhalter

Affiliations

Soon will be listed here.

Abstract

A heterogeneous group of patients suffering from adenomatous polyposis coli (APC) were evaluated by clinical and genetic investigations for the first time in Austria. The patients belonged to eight unrelated APC families. In six families several family members were affected with APC, and linkage analysis with highly informative markers was used to estimate the risk of single individuals in these families to develop APC. All index patients were also tested for the most frequent mutation in the APC gene (mutation cluster region, exon 15). Clinical investigations included ophthalmologic tests for congenital hypertrophy of retinal pigment epithelium and colonoscopy. According to DNA analysis, 5 of 19 at-risk individuals had to be considered to be at high risk of having inherited the disease. Four of them underwent proctocolectomy, one patient at risk is under colonoscopic surveillance. The predictive value of indirect genotype analyses reached 83.3%; direct mutation analyses allowed risk estimation in 50% of cases. Ophthalmologic investigation was informative in 75% of the families. Direct and indirect genotyping using a panel of highly polymorphic, closely linked microsatellite markers is a valuable, rapid, reliable method for establishing a presymptomatic diagnosis of APC, especially in families in which more than one affected individual is available for analysis. With regard to the onset of APC and extracolonic manifestations, the variability of APC demands clinical investigations in addition to the molecular tests for all patients and their first-degree relatives.

Citing Articles

Quality in genetic counselling for presymptomatic testing--clinical guidelines for practice across the range of genetic conditions.

Skirton H, Goldsmith L, Jackson L, Tibben A Eur J Hum Genet. 2012; 21(3):256-60.

PMID: 22892534 PMC: 3573206. DOI: 10.1038/ejhg.2012.174.

References

Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A, Miki Y . Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci U S A. 1992; 89(10):4452-6. PMC: 49100. DOI: 10.1073/pnas.89.10.4452. View

Eckert W, Jung C, Wolff G . Presymptomatic diagnosis in families with adenomatous polyposis using highly polymorphic dinucleotide CA repeat markers flanking the APC gene. J Med Genet. 1994; 31(6):442-7. PMC: 1049920. DOI: 10.1136/jmg.31.6.442. View

Petersen G . Knowledge of the adenomatous polyposis coli gene and its clinical application. Ann Med. 1994; 26(3):205-8. DOI: 10.3109/07853899409147891. View

Romania A, Zakov Z, McGannon E, Schroeder T, Heyen F, Jagelman D . Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Ophthalmology. 1989; 96(6):879-84. DOI: 10.1016/s0161-6420(89)32822-3. View

Moore A, Maher E, Koch D, Charles S . Incidence and significance of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in familial adenomatous polyposis coli (FAPC). Ophthalmic Paediatr Genet. 1992; 13(2):67-71. DOI: 10.3109/13816819209087606. View

Bodmer W, Bailey C, Bodmer J, Bussey H, Ellis A, Gorman P . Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987; 328(6131):614-6. DOI: 10.1038/328614a0. View

Friedl W, Mandl M, Sengteller M . Single-step screening method for the most common mutations in familial adenomatous polyposis. Hum Mol Genet. 1993; 2(9):1481-2. DOI: 10.1093/hmg/2.9.1481. View

Bulow S . Familial polyposis coli. Dan Med Bull. 1987; 34(1):1-15. View

Spirio L, Joslyn G, Nelson L, Leppert M, White R . A CA repeat 30-70 KB downstream from the adenomatous polyposis coli (APC) gene. Nucleic Acids Res. 1991; 19(22):6348. PMC: 329171. DOI: 10.1093/nar/19.22.6348. View

10.

Petersen G, Slack J, Nakamura Y . Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-64. DOI: 10.1016/0016-5085(91)90666-9. View

11.

Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H . Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991; 66(3):589-600. DOI: 10.1016/0092-8674(81)90021-0. View

12.

Shibata D, Arnheim N, Martin W . Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction. J Exp Med. 1988; 167(1):225-30. PMC: 2188813. DOI: 10.1084/jem.167.1.225. View

13.

Breukel C, Tops C, Ras E, Khan P . Mspl RFLP at the D5S122 locus tightly linked to APC. Nucleic Acids Res. 1991; 19(3):685. PMC: 333680. DOI: 10.1093/nar/19.3.685-a. View

14.

Evans D, Guy S, Thakker N, Armstrong J, Dodd C, Davies D . Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis. Gut. 1993; 34(10):1389-93. PMC: 1374547. DOI: 10.1136/gut.34.10.1389. View

15.

Tops C, Wijnen J, Griffioen G, von Leeuwen I, Vasen H, den Hartog Jager F . Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. Lancet. 1989; 2(8676):1361-3. DOI: 10.1016/s0140-6736(89)91968-5. View

16.

Bulow S . Clinical features in familial polyposis coli. Results of the Danish Polyposis Register. Dis Colon Rectum. 1986; 29(2):102-7. DOI: 10.1007/BF02555389. View

17.

Bulow S, Holm N, Hauge M . The incidence and prevalence of familial polyposis coli in Denmark. Scand J Soc Med. 1986; 14(2):67-74. DOI: 10.1177/140349488601400205. View

18.

Dunlop M, Wyllie A, Steel C, Piris J, Evans H . Linked DNA markers for presymptomatic diagnosis of familial adenomatous polyposis. Lancet. 1991; 337(8737):313-6. DOI: 10.1016/0140-6736(91)90940-q. View

19.

Kraus C, Ballhausen W . Two intragenic polymorphisms of the APC-gene detected by PCR and enzymatic digestion. Hum Genet. 1992; 88(6):705-6. DOI: 10.1007/BF02265305. View

20.

Mareni C, Stella A, Origone P, Susca F, Montera M, Lonoce A . Linkage studies in Italian families with familial adenomatous polyposis. Hum Genet. 1993; 90(5):545-50. DOI: 10.1007/BF00217456. View