TY - JOUR
T1 - Classic, atypically severe and neonatal Marfan syndrome
T2 - Twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40
AU - Tiecke, Frank
AU - Katzke, Stefanie
AU - Booms, Patrick
AU - Robinson, Peter N.
AU - Neumann, Luitgard
AU - Godfrey, Maurice
AU - Mathews, Kurt R.
AU - Scheuner, Maren
AU - Hinkel, Georg Klaus
AU - Brenner, Rolf E.
AU - Hövels-Gürich, Hedwig H.
AU - Hagemeier, Christian
AU - Fuchs, Josefine
AU - Skovby, Flemming
AU - Rosenberg, Thomas
PY - 2001
Y1 - 2001
N2 - Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32, mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.
AB - Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32, mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.
KW - Fibrillin
KW - Genotype-phenotype correlation
KW - Marfan syndrome
KW - Temperature-gradient gel electrophoresis (TGGE)
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U2 - 10.1038/sj.ejhg.5200582
DO - 10.1038/sj.ejhg.5200582
M3 - Article
C2 - 11175294
AN - SCOPUS:0035141446
SN - 1018-4813
VL - 9
SP - 13
EP - 21
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 1
ER -