ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE).
Hum Mutat
; 24(5): 438-9, 2004 Nov.
Article
en En
| MEDLINE
| ID: mdl-15459974
ABSTRACT
Pseudoxanthoma elasticum (PXE) is a genetic disorder, characterized by cutaneous, ocular and cardiovascular clinical symptoms, caused by mutations in a gene (ABCC6) that encodes for MRP6 (Multidrug Resistance associated Protein 6), an ATP-binding cassette membrane transporter. The ABCC6 gene was sequenced in 38 unrelated PXE Italian families. The mutation detection rate was 82.9%. Mutant alleles occurred in homozygous, compound heterozygous and heterozygous forms, however the great majority of patients were compound heterozygotes. Twenty-three different mutations were identified, among which 11 were new. Fourteen were missense (61%); five were nonsense (22%); two were frameshift (8.5%) and two were putative splice site mutations (8.5%). The great majority of mutations were located from exon 24 to 30, exon 24 being the most affected. Among the others, exons 9 and 12 were particularly involved. Almost all mutations were located in the intracellular site of MRP6. A positive correlation was observed between patient's age and severity of the disorder, especially for eye alterations. The relevant heterogeneity in clinical manifestations between patients with identical ABCC6 mutations, even within the same family, seems to indicate that, apart from PXE causative mutations, other genes and/or metabolic pathways might influence the clinical expression of the disorder.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Seudoxantoma Elástico
/
Proteínas Asociadas a Resistencia a Múltiples Medicamentos
/
Mutación
Límite:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia