Unknown

Dataset Information

0

Combination of linkage mapping and microarray-expression analysis identifies NF-kappaB signaling defect as a cause of autosomal-recessive mental retardation.

ABSTRACT: Autosomal-recessive inheritance accounts for nearly 25% of nonsyndromic mental retardation (MR), but the extreme heterogeneity of such conditions markedly hampers gene identification. Combining autozygosity mapping and RNA expression profiling in a consanguineous Tunisian family of three MR children with mild microcephaly and white-matter abnormalities identified the TRAPPC9 gene, which encodes a NF-kappaB-inducing kinase (NIK) and IkappaB kinase complex beta (IKK-beta) binding protein, as a likely candidate. Sequencing analysis revealed a nonsense variant (c.1708C>T [p.R570X]) within exon 9 of this gene that is responsible for an undetectable level of TRAPPC9 protein in patient skin fibroblasts. Moreover, TNF-alpha stimulation assays showed a defect in IkBalpha degradation, suggesting impaired NF-kappaB signaling in patient cells. This study provides evidence of an NF-kappaB signaling defect in isolated MR.

SUBMITTER: Philippe O 

PROVIDER: S-EPMC2795800 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Combination of linkage mapping and microarray-expression analysis identifies NF-kappaB signaling defect as a cause of autosomal-recessive mental retardation.

Philippe Orianne O   Rio Marlène M   Carioux Astrid A   Plaza Jean-Marc JM   Guigue Philippe P   Molinari Florence F   Boddaert Nathalie N   Bole-Feysot Christine C   Nitschke Patrick P   Smahi Asma A   Munnich Arnold A   Colleaux Laurence L  

American journal of human genetics 20091201 6

Autosomal-recessive inheritance accounts for nearly 25% of nonsyndromic mental retardation (MR), but the extreme heterogeneity of such conditions markedly hampers gene identification. Combining autozygosity mapping and RNA expression profiling in a consanguineous Tunisian family of three MR children with mild microcephaly and white-matter abnormalities identified the TRAPPC9 gene, which encodes a NF-kappaB-inducing kinase (NIK) and IkappaB kinase complex beta (IKK-beta) binding protein, as a lik  ...[more]

Similar Datasets

Genomics A defect in the ionotropic glutamate receptor 6 gene (GRIK2) causes autosomal recessive mental retardation
2007-07-04 | GSE7886 | GEO
Unknown A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.
| S-EPMC2651624 | biostudies-literature
Unknown A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation.
| S-EPMC2227928 | biostudies-literature
Unknown Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome).
| S-EPMC2849979 | biostudies-literature
Unknown A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability.
| S-EPMC4326716 | biostudies-literature
Unknown Premature chromosome condensation in humans associated with microcephaly and mental retardation: a novel autosomal recessive condition.
| S-EPMC379095 | biostudies-other
Unknown CC2D2A, encoding a coiled-coil and C2 domain protein, causes autosomal-recessive mental retardation with retinitis pigmentosa.
| S-EPMC2427291 | biostudies-literature
Unknown The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation.
| S-EPMC3914474 | biostudies-literature
Unknown Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.
| S-EPMC2925262 | biostudies-literature
Unknown Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family.
| S-EPMC5393418 | biostudies-literature