Exploring the potential role of disease-causing mutation in a gene desert: duplication of noncoding elements 5' of GRIA3 is associated with GRIA3 silencing and X-linked intellectual disability.
Hum Mutat
; 33(2): 355-8, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-22124977
ABSTRACT
GRIA3 encodes glutamate receptor ionotropic AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subunit 3 and has been previously involved in X-linked intellectual disability (ID). We report on a male proband with ID and epilepsy associated with a duplication mapping within a gene desert, 874-kb upstream of the GRIA3 gene. This 970-kb duplication is maternally inherited. The proband's mother has a skewed X chromosome-inactivation pattern in agreement with her normal cognitive function. Quantitative polymerase chain reaction analysis indicates absence of GRIA3 mRNA in the proband lymphocytes relative to a wild-type control. Centromeric to the duplicated region, comparative genomic analysis showed a 2268-bp evolutionarily conserved region that could be a critical transcription factor binding-site for GRIA3 expression. The repositioning of distant-acting sequences, rather a missense/nonsense mutation, is considered to be causative for GRIA3-linked ID. This study illustrates the importance of high-resolution array-Comparative Genomic Hybridization analysis in exploring the potential role of disease-causing mutation in functional noncoding sequences.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Receptores AMPA
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Regiones no Traducidas 5'
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Duplicación de Gen
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Silenciador del Gen
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Enfermedades Genéticas Ligadas al Cromosoma X
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Discapacidad Intelectual
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Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Child
/
Humans
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Male
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia