与新形式智力障碍有关的基因

        4月11日的爱思唯尔期刊《美国人类遗传学杂志》（American Journal of Human Genetics）刊登了加拿大多伦多大学精神健康中心的一项最新研究。科学家发现了一种新的形式智力障碍，其表现形式为伴有视网膜色素变性的智力发育迟缓。同时，研究人员也确定了与此有关的基因CC2D2A。

        智力障碍即智力低下，是严重危害儿童身心健康的一类世界性疾患，男性患此病的比例较高。目前发现的绝大多数智力障碍都与X染色体有关，而本研究发现的突变是在常染色体上。研究发现CC2D2A突变会引起与蛋白钙离子结合的结构域的缩小，此突变导致了细胞功能的不完善，结果造成伴有视网膜色素变性的智力发育迟缓。视网膜色素变性是一种具有明显遗传倾向的慢性、进行性视网膜色素上皮和光感受器的变性疾病。

       研究人员认为，该研究进展将有助于进一步研究脑发育过程，同时将有助于采取新的方法诊断和治疗智力障碍。(科学网 于乃森/编译)

原始出处：

American Journal of Human Genetics，doi:10.1016/j.ajhg.2008.01.021，Abdul Noor, Muhammad Ayub

CC2D2A, Encoding A Coiled-Coil and C2 Domain Protein, Causes Autosomal-Recessive Mental Retardation with Retinitis Pigmentosa

Abdul Noor¹, Christian Windpassinger^1, 2, Megha Patel¹, Beata Stachowiak¹, Anna Mikhailov¹, Matloob Azam³, Muhammad Irfan⁴, Zahid Kamal Siddiqui⁵, Farooq Naeem⁶, Andrew D. Paterson⁷, Muhammad Lutfullah⁸, John B. Vincent^1, ,   and Muhammad Ayub⁹

Corresponding author

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 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.