The fibrillin gene (FBN1) is the disease locus for Marfan syndrome. This disorder shows a high degree of clinical and allelic heterogeneity. Direct mutation screening has proven difficult and inefficient and at present cannot be utilized for routine analysis. In familial cases linkage analysis represents a useful tool for molecular diagnosis. We have determined the allelic frequencies of 5 polymorphic markers within the FBN1 locus in the Italian population and have successfully employed them for prenatal diagnosis and resolution of clinically equivocal cases.

1.
Kainulainen K, Karttunen L, Puhakka L, Sakai LY, Peltonen L: Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med 1990;323:935–939.
2.
Lee B, Godfrey M, Vitale E, Hori H, Mattei MG, Sarfarazi M, Tsipouras P, Ramirez F, Hollister DW: Linkage of Marfan syndrome and a phenotypically related disorder to two fibrillin genes. Nature 1991;352:330–334.
3.
Maslen CL, Corson GM, Maddox BK, Glanville RW, Sakai LY: Partial sequence of a candidate gene for the Marfan syndrome. Nature 1991;352:334–337.
4.
Tsipouras P: Marfan syndrome: Light at the end of the tunnel? Am J Hum Genet 1990;46:643–645.
5.
Hayward C, Brock DJH: Fibrillin 1 mutations in Marfan syndrome and other type 1 fibrillinopathies. Hum Mutat 1997;10:415–423.
6.
Collod G, Babron MC, Jondeau G, Coulon M, Weissenbach J, Dubourg O, Bourdarias JP, Bonaiti Pellié C, Junien C, Boileau C: A second locus for Marfan syndrome maps to chromosome 3p24.2-p25. Nat Genet 1994;8:264–268.
7.
De Paepe A, Devereux RB, Dietz HC, Hennekam RCM, Pyeritz RE: Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62:417–426.
8.
Pereira L, D’Alessio M, Ramirez F, Lynch JR, Sykes B, Pangilinan T, Bonadio J: Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet 1993;2:961–968.
9.
Pereira L, Levran O, Ramirez F, Lynch JR, Sykes B, Pyeritz RE, Dietz HC: A molecular approach to the stratification of cardiovascular risk in families with Marfan syndrome. N Engl J Med 1994;331:148–153.
10.
Tynan K, Comeau K, Pearson M, Wilgenbus P, Levitt D, Gasner C, Berg MA, Miller DC, Francke U: Mutation screening of complete fibrillin 1 coding sequence: Report of five new mutations including two in 8-cysteine domains. Hum Mol Genet 1993;2:1813–1821.
11.
Slatkin M: Linkage disequilibrium in growing and stable populations. Genetics 1994;137:331–336.
12.
Guo S, Thompson E: Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics 1992;48:361–372.
13.
Raymond M, Rousset F: An exact test for population differentiation. Evolution 1995;49:1280–1283.
14.
Hewett D, Lynch J, Child A, Firth H, Sykes B: Differential allelic expression of a fibrillin gene (FBN1) in patients with Marfan syndrome. Am J Hum Genet 1994;55:447–452.
15.
Karttunen L, Raghunath M, Lonnqvist L, Peltonen L: A compound heterozygous Marfan patient: Two defective fibrillin alleles result in a lethal phenotype. Am J Hum Genet 1994;55:1083–1091.
16.
Piazza A, Mayr WR, Contu L, Amoroso A, Borelli I, Curtoni ES, Marcello C, Moroni A, Olivetti E, Richiardi P, Ceppellini R: Genetic and population structure of four Sardinian villages. Ann Hum Genet 1985;49:47–63.
17.
Hollister DW, Godfrey M, Sakai LY, Pyeritz RE: Immunohistologic abnormalities of the microfibrillar fiber system in the Marfan syndrome. N Engl J Med 1990;323:152–159.
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