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Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation

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Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation. / Palz, M; Tiecke, F; Booms, P; Göldner, B; Rosenberg, T; Fuchs, J; Skovby, F; Schumacher, H; Kaufmann, U C; von Kodolitsch, Y; Nienaber, C A; Leitner, C; Katzke, S; Vetter, B; Hagemeier, C; Robinson, P N.

In: Am J Med Genet, Vol. 91, No. 3, 20.03.2000, p. 212-221.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Palz, M, Tiecke, F, Booms, P, Göldner, B, Rosenberg, T, Fuchs, J, Skovby, F, Schumacher, H, Kaufmann, UC, von Kodolitsch, Y, Nienaber, CA, Leitner, C, Katzke, S, Vetter, B, Hagemeier, C & Robinson, PN 2000, 'Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation', Am J Med Genet, vol. 91, no. 3, pp. 212-221. https://doi.org/10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3

APA

Palz, M., Tiecke, F., Booms, P., Göldner, B., Rosenberg, T., Fuchs, J., Skovby, F., Schumacher, H., Kaufmann, U. C., von Kodolitsch, Y., Nienaber, C. A., Leitner, C., Katzke, S., Vetter, B., Hagemeier, C., & Robinson, P. N. (2000). Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation. Am J Med Genet, 91(3), 212-221. https://doi.org/10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3

Vancouver

Palz M, Tiecke F, Booms P, Göldner B, Rosenberg T, Fuchs J et al. Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation. Am J Med Genet. 2000 Mar 20;91(3):212-221. https://doi.org/10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3

Bibtex

@article{0d989afec2794c0995ba1a27455e2d1f,
title = "Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation",
abstract = "Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the {"}hot spots{"} for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.",
keywords = "Adolescent, Adult, Child, Child, Preschool, DNA Mutational Analysis, Exons, Female, Fibrillin-1, Fibrillins, Genotype, Humans, Male, Marfan Syndrome/genetics, Microfilament Proteins/genetics, Mutation, Phenotype, Polymerase Chain Reaction, Protein Structure, Tertiary",
author = "M Palz and F Tiecke and P Booms and B G{\"o}ldner and T Rosenberg and J Fuchs and F Skovby and H Schumacher and Kaufmann, {U C} and {von Kodolitsch}, Y and Nienaber, {C A} and C Leitner and S Katzke and B Vetter and C Hagemeier and Robinson, {P N}",
note = "Copyright 2000 Wiley-Liss, Inc.",
year = "2000",
month = mar,
day = "20",
doi = "10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3",
language = "English",
volume = "91",
pages = "212--221",
number = "3",

}

RIS

TY - JOUR

T1 - Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation

AU - Palz, M

AU - Tiecke, F

AU - Booms, P

AU - Göldner, B

AU - Rosenberg, T

AU - Fuchs, J

AU - Skovby, F

AU - Schumacher, H

AU - Kaufmann, U C

AU - von Kodolitsch, Y

AU - Nienaber, C A

AU - Leitner, C

AU - Katzke, S

AU - Vetter, B

AU - Hagemeier, C

AU - Robinson, P N

N1 - Copyright 2000 Wiley-Liss, Inc.

PY - 2000/3/20

Y1 - 2000/3/20

N2 - Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

AB - Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - DNA Mutational Analysis

KW - Exons

KW - Female

KW - Fibrillin-1

KW - Fibrillins

KW - Genotype

KW - Humans

KW - Male

KW - Marfan Syndrome/genetics

KW - Microfilament Proteins/genetics

KW - Mutation

KW - Phenotype

KW - Polymerase Chain Reaction

KW - Protein Structure, Tertiary

U2 - 10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3

DO - 10.1002/(sici)1096-8628(20000320)91:3<212::aid-ajmg12>3.0.co;2-3

M3 - SCORING: Journal article

C2 - 10756346

VL - 91

SP - 212

EP - 221

IS - 3

ER -