A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

Abstract

Chromosome duplications are found in about 2% of subjects with a typical chromosomal phenotype but their frequency is likely to be higher, as suggested by the first array-CGH data. According to the orientation of the duplicated segment, duplications may be in tandem or inverted. The latter are usually associated with a distal deletion. We studied a de novo 2.3 Mb inverted duplication of 8q24.3 without apparently associated deletion in a subject with profound psychomotor retardation, idiopathic epilepsy and growth delay. In spite of its small size, the presence of the rearrangement was suspected on standard karyotypes (approximately 400 bands) and later confirmed by Fluorescent in situ hybridization (FISH) analysis. We hypothesize that the GRINA gene, a glutamate binding subunit of NMDA receptor ion channel lying within the duplicated segment, may be responsible for the epilepsy. This paper confirms that small subtelomeric de novo duplications may be responsible for mental retardation, facial dysmorphisms and/or congenital malformations, although their presence may be overlooked by FISH analysis.

Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23‐pter

“…Many other examples of inverted duplication deletions have now been reported, suggesting that the mechanism responsible for the inv dup(8p) can be generalized to all inverted duplications [Bonaglia et al, 2000;Ciccone et al, 2006]. However, Bonaglia et al [2005] could not demonstrate, nor exclude, in an atypical inv dup(8q) without apparently associated deletion, the presence of the distal deletion associated to the duplication, as in the 8q24.3 region, two genome sequence gaps are still present. In our rearrangement, a single-copy region between the deleted and duplicated regions, usually described in the inv dup del chromosomes, was not detected.…”

TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis

“…34 Interestingly, human TMBIM3 gene location maps close to a locus genetically linked with epilepsy. 35 A viable tmbim3 knock-out mice was recently generated confirming the neuronal expression of TMBIM3 in mice. 36 However, no functional analysis of TMBIM3 KO mice was performed.…”

Masked complex chromosome rearrangement in a child thought to have del(8qter) as the sole cytogenetic abnormality

“…Deletions/duplications of 8q24 have been rarely reported in the literature and, to the best of our knowledge, only four papers have described this chromosome rearrangement (Eussen et al, 2000;Bonaglia et al, 2005;Gradek et al, 2006;Tokutomi et al, 2007) in patients with phenotypes different from that of our case. Bonaglia et al (2005) and Eussen et al (2000) both described a duplication of chromosome 8q24.3: the former associated with epilepsy and severe mental retardation and the latter with tuberous sclerosis complex, adult polycystic kidney disease, and hypomelanosis of Ito.…”

“…Bonaglia et al (2005) and Eussen et al (2000) both described a duplication of chromosome 8q24.3: the former associated with epilepsy and severe mental retardation and the latter with tuberous sclerosis complex, adult polycystic kidney disease, and hypomelanosis of Ito. On the other hand, Gradek et al (2006) and Tokutomi et al (2007) reported a deletion of the region 8q24.3 K qter: the first present in a mosaic patient with mild phenotype and the second in a girl with hepatic focal nodular hyperplasia.…”