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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Noor, A; Windpassinger, C; Patel, M; Stachowiak, B; Mikhailov, A; Azam, M; Irfan, M; Siddiqui, ZK; Naeem, F; Paterson, AD; Lutfullah, M; Vincent, JB; Ayub, M.
CC2D2A, encoding a coiled-coil and C2 domain protein, causes autosomal-recessive mental retardation with retinitis pigmentosa.
Am J Hum Genet. 2008; 82(4):1011-1018
Doi: 10.1016/j.ajhg.2008.01.021
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- Co-authors Med Uni Graz
- Windpassinger Christian
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- Abstract:
- Autosomal-recessive inheritance is believed to be relatively common in mental retardation (MR), although only four genes for nonsyndromic autosomal-recessive mental retardation (ARMR) have been reported. In this study, we ascertained a consanguineous Pakistani family with ARMR in four living individuals from three branches of the family, plus an additional affected individual later identified as a phenocopy. Retinitis pigmentosa was present in affected individuals, but no other features suggestive of a syndromic form of MR were found. We used Affymetrix 500K microarrays to perform homozygosity mapping and identified a homozygous and haploidentical region of 11.2 Mb on chromosome 4p15.33-p15.2. Linkage analysis across this region produced a maximum two-point LOD score of 3.59. We sequenced genes within the critical region and identified a homozygous splice-site mutation segregating in the family, within a coiled-coil and C2 domain-containing gene, CC2D2A. This mutation leads to the skipping of exon 19, resulting in a frameshift and a truncated protein lacking the C2 domain. Conservation analysis for CC2D2A suggests a functional domain near the C terminus as well as the C2 domain. Preliminary functional studies of CC2D2A suggest a possible role in Ca(2+)-dependent signal transduction. Identifying the function of CC2D2A, and a possible common pathway with CC2D1A, in correct neuronal development and functioning may help identify possible therapeutic targets for MR.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Amino Acid Sequence -
- Animals -
- Calcium - metabolism
- Child, Preschool -
- Chromosome Mapping -
- Chromosomes, Human, Pair 4 - genetics
- Consanguinity -
- Exons - genetics
- Female -
- Frameshift Mutation -
- Haplotypes -
- Homozygote -
- Humans -
- Lod Score -
- Male -
- Mental Retardation - genetics
- Molecular Sequence Data -
- Oligonucleotide Array Sequence Analysis -
- Pakistan -
- Pedigree -
- Protein Structure, Tertiary - genetics
- Proteins - genetics
- RNA Splicing - genetics
- Retinitis Pigmentosa - genetics