Marfan syndrome caused by a mutation in FBN1 that gives rise to cryptic splicing and a 33 nucleotide insertion in the coding sequence.
Hum Genet
; 109(4): 416-20, 2001 Oct.
Article
en En
| MEDLINE
| ID: mdl-11702223
We have studied a patient with Marfan syndrome whose mutation was not detected by heteroduplex analysis. Primary cultured patient fibroblasts were metabolically labelled and found to secrete fibrillin-1 defectively when compared with an age-matched control. Sequencing of patient cDNA, isolated by reverse transcription-polymerase chain reaction of patient fibroblast RNA, detected a 33-bp insertion. The reading frame of the mutant allele was maintained and predicted the insertion of 11 amino acids at the beginning of calcium-binding epidermal growth factor-like domain 29. Direct sequencing of genomic DNA detected a heterozygous G+1-->A transversion in intron 46 of FBN1. The 11 amino acid insertion was the consequence of the usage of a cryptic splice site 33-bp downstream of the mutation. This is the first reported case of a splicing defect in FBN1 leading to the production of a full-length fibrillin-1 transcript containing a large amino acid insertion.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Exones
/
Mutagénesis Insercional
/
Empalme Alternativo
/
Síndrome de Marfan
/
Proteínas de Microfilamentos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Hum Genet
Año:
2001
Tipo del documento:
Article
Pais de publicación:
Alemania