Clinical and genetic studies in a family with a new splice-site mutation in the choroideremia gene.
Mol Vis
; 20: 325-33, 2014.
Article
en En
| MEDLINE
| ID: mdl-24672218
ABSTRACT
PURPOSE:
To describe the clinical and molecular findings of an Italian family with a new mutation in the choroideremia (CHM) gene.METHODS:
We performed a comprehensive ophthalmologic examination, fundus photography, macular optical coherence tomography, perimetry, electroretinography, and fluorescein angiography in an Italian family. The clinical diagnosis was supported by western blot analysis of lymphoblastoid cell lines from patients with CHM and carriers, using a monoclonal antibody against the 415 C-terminal amino acids of Rab escort protein-1 (REP-1). Sequencing of the CHM gene was undertaken on genomic DNA from affected men and carriers; the RNA transcript was analyzed with reverse transcriptase-PCR.RESULTS:
The affected men showed a variability in the rate of visual change and in the degree of clinical and functional ophthalmologic involvement, mainly age-related, while the women displayed aspecific areas of chorioretinal degeneration. Western blot did not show a detectable amount of normal REP-1 protein in affected men who were hemizygous for a novel mutation, c.819+2T>A at the donor splicing site of intron 6 of the CHM gene; the mutation was confirmed in heterozygosity in the carriers.CONCLUSIONS:
Western blot of the REP-1 protein confirmed the clinical diagnosis, and molecular analysis showed the new in-frame mutation, c.819+2T>A, leading to loss of function of the REP-1 protein. These results emphasize the value of a diagnostic approach that correlates genetic and ophthalmologic data for identifying carriers in families with CHM. An early diagnosis might be crucial for genetic counseling of this type of progressive and still untreatable disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Coroideremia
/
Sitios de Empalme de ARN
/
Proteínas Adaptadoras Transductoras de Señales
/
Mutación
Tipo de estudio:
Prognostic_studies
/
Screening_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Mol Vis
Asunto de la revista:
BIOLOGIA MOLECULAR
/
OFTALMOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Italia