Novel approach to the molecular diagnosis of Marfan syndrome: application to sporadic cases and in prenatal diagnosis.

Autor: Toudjarska I; Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA., Kilpatrick MW, Lembessis P, Carra S, Harton GL, Sisson ME, Black SH, Stern HJ, Gelman-Kohan Z, Shohat M, Tsipouras P
Jazyk: angličtina
Zdroj: American journal of medical genetics [Am J Med Genet] 2001 Apr 01; Vol. 99 (4), pp. 294-302.
DOI: 10.1002/ajmg.1174
Abstrakt: Marfan syndrome is an autosomal dominant disorder affecting the skeletal, ocular, and cardiovascular systems. Defects in the gene that encodes fibrillin-1 (FBN1), the main structural component of the elastin-associated microfibrils, are responsible for the disorder. Molecular diagnosis in families with Marfan syndrome can be undertaken by using intragenic FBN1 gene markers to identify and track the disease allele. However, in sporadic cases, which constitute up to 30% of the total, DNA-based diagnosis cannot be performed using linked markers but rather requires the identification of the specific FBN1 gene mutation. Due to the size and complexity of the FBN1 gene, identification of a causative Marfan syndrome mutation is not a trivial undertaking. Herein, we describe a comprehensive approach to the molecular diagnosis of Marfan syndrome that relies on the direct analysis of the FBN1 gene at the cDNA level and detects both coding sequence mutations and those leading to exon-skipping, which are often missed by analysis at the genomic DNA level. The ability to consistently determine the specific FBN1 gene mutation responsible for a particular case of Marfan syndrome allows both prenatal and pre-implantation diagnosis, even in sporadic instances of the disease.
(Copyright 2001, Wiley-Liss. Inc.)
Databáze: MEDLINE
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