TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies.
Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome (MFS), an autosomal dominant heritable disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. FBN1 mutations have also been identified in a series of related disorders of connective tissue collectively termed type-1 fibrillinopathies. We have developed temperature-gradient gel electrophoresis (TGGE) assays for all 65 FBN1 exons, screened 126 individuals with MFS, other type-1 fibrillinopathies, and other potentially related disorders of connective tissue for FBN1 mutations, and identified a total of 53 mutations, of which 33 are described here for the first time. Several mutations were identified in individuals with fibrillinopathies other than classic Marfan syndrome, including aneurysm of the ascending aorta with only minor skeletal anomalies, and several individuals with only skeletal and ocular involvement. The mutation detection rate in this study was 42% overall, but was only 12% in individuals not fulfilling the diagnostic criteria for MFS, suggesting that clinical overdiagnosis is one reason for the low detection rate observed for FBN1 mutation analysis.
Institute of Medical Genetics, Charité University Hospital, Berlin, Germany.
Stefanie
S
Katzke
Patrick
P
Booms
Frank
F
Tiecke
Monika
M
Palz
Angelika
A
Pletschacher
Seval
S
Türkmen
Luitgard M
LM
Neumann
Reinhard
R
Pregla
Christa
C
Leitner
Cornelia
C
Schramm
Peter
P
Lorenz
Christian
C
Hagemeier
Josefine
J
Fuchs
Flemming
F
Skovby
Thomas
T
Rosenberg
Peter N
PN
Robinson
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D005091:Exons / Q000235:genetics*; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D054392:Adipokines
D004247:DNA; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines