Aberrant GRIA3 Transcripts With Multi-Exon Duplications in a Family With X-Linked Mental Retardation

作者：Bonnet C; Leheup B; Beri M; Philippe C; Gregoire M J; Jonveaux P^*

来源：American Journal of Medical Genetics, Part A, 2009, 149A(6): 1280-1289.

DOI：10.1002/ajmg.a.32858

• X-linked mental retardation
• GRIA3
• duplication
• array-CGH

Investigation of chromosomal rearrangements in patients with mental retardation (MR) is particularly informative in the search for novel genes involved in MR. We report on a family with a genomic duplication at Xq25 identified by oligo array-CGH. Further characterization showed a partial tandem duplication of GRIA3 extending from exon 1 to exon 12. This duplication is present in two brothers with MR and on one allele in their sister with normal phenotype and completely skewed X-chromosome inactivation. The duplication is inherited from the mother, whose cognitive level is low and X-chromosome inactivation is random. This is the second family with partial duplication of GRIA3 associated with MR. GRIA3 expression studies in our case demonstrated a new mechanism for GRIA3 dysfunction with the presence of aberrant GRIA3 transcripts carrying multi-exon duplications leading to a frameshift. Our study gives additional support to the implication of GRIA3 in X-linked MR.

• 出版日期2009-6