Department Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Am J Med Genet A. 2011 Aug;155A(8):1976-80. doi: 10.1002/ajmg.a.34077. Epub 2011 Jul 7.
The genetic basis of autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to suspect that the number of underlying gene defects may well go beyond 1,000. To date, however, only less than 10 genes have been implicated in non-specific/non-syndromic ARMR (NS-ARMR). As part of an ongoing systematic study aiming to identify further ARMR genes, we investigated a consanguineous family with three patients with NS-ARMR. By linkage analysis and subsequent mutation screening we identified a novel nonsense mutation (c.163C > T [p.Q55X]) in the second exon of the TUSC3 gene. This is the third MR causing defect in TUSC3 to be described and the second independent mutation in this gene in a cohort of more than 200 ARMR families from the Iranian population. This argues for a more prominent role of TUSC3 in the etiology of this genetically heterogeneous disorder as compared to most of the other so far identified ARMR genes.
常染色体隐性智力障碍（ARMR）的遗传基础极其多样化，有理由怀疑潜在的基因缺陷数量可能远远超过 1000 个。然而，迄今为止，只有不到 10 个基因与非特异性/非综合征性 ARMR（NS-ARMR）有关。作为正在进行的旨在鉴定更多 ARMR 基因的系统研究的一部分，我们调查了一个患有 NS-ARMR 的近亲家庭。通过连锁分析和随后的突变筛查，我们在 TUSC3 基因的第二个外显子中发现了一个新的无义突变（c.163C>T [p.Q55X]）。这是 TUSC3 中第三个导致智力障碍的缺陷，也是在来自伊朗人群的 200 多个 ARMR 家族的队列中发现的第二个独立突变。这表明与迄今为止鉴定的大多数其他 ARMR 基因相比，TUSC3 在这种遗传异质性疾病的发病机制中发挥着更为重要的作用。
