Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal recessive Alport syndrome.
Hum Mol Genet
; 4(4): 675-9, 1995 Apr.
Article
en En
| MEDLINE
| ID: mdl-7633417
ABSTRACT
Alport syndrome is a mainly X-linked hereditary disease of basement membranes characterized by progressive renal failure, deafness, and ocular lesions. The alpha 3(IV) and alpha 4(IV) collagen genes have been recently shown to be involved in the less frequent autosomal recessive form. When screening lymphocyte COL4A3 mRNAs from Alport patients, we found a mutant whose transcripts were disrupted by a 74 bp insertion at the junction of exons IV or V and VI. The insertion derives from an antisense Alu element in COL4A3 intron V, which has been spliced into the alpha 3(IV) mRNA due to a G to T transversion activating a cryptic acceptor splice site in this Alu element. There is complete segregation of this mutation with the disease in the family. Our findings provide the first evidence for the pathogenic role of abnormal splicing of COL4A3. Moreover, we demonstrate the superiority of mutation screening at the mRNA level to detect a hitherto poorly recognized mutation mechanism in humans, splice-mediated insertion of an Alu fragment into a coding sequence.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Secuencias Repetitivas de Ácidos Nucleicos
/
Empalme del ARN
/
Colágeno
/
Genes Recesivos
/
Nefritis Hereditaria
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
1995
Tipo del documento:
Article
País de afiliación:
Francia