CC2D2A
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- 作者：Abdul Noor ; Christian Windpassinger ; Megha Patel ; Beata Stachowiak ; Anna Mikhailov ; Matloob Azam ; Muhammad Irfan ; Zahid Kamal Siddiqui ; Farooq Naeem ; Andrew D. Paterson ; Muhammad Lutfullah ; John B. Vincent ; Muhammad Ayub
- 刊名：The American Journal of Human Genetics
- 出版年：2008
- 出版时间：11 April 2008
- 年：2008
- 卷：82
- 期：4
- 页码：1011-1018
- 全文大小：1236 K
文摘
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 Ca2+-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.