Inserm, U930, Tours, France.
World J Biol Psychiatry. 2009;10(4 Pt 3):1030-6. doi: 10.1080/15622970802627455.
The high concordance for autism symptoms in monozygotic twin-pairs compared to di-zygotic twins and/or non-twin sib-ships suggests a high genetic determinism in autism. Those results have hypothesized multi-factorial determinism in accordance with family studies and mathematical models. However, linkage and association or candidate gene strategies have failed to-date to identify clearly involved mechanisms. Mental retardation (MR) is known as frequently associated to autism. Multiplex XLMR pedigrees have been reported with only one mutated patient having autism and MR: different X-located MR genes have been shown to be involved (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be "autism genes". Tuberous sclerosis studies and report of numerous autosomal domains shown deleted in MR-autistic subjects suggest that several autosomal dominant (AD) genes could be also involved in MR with autism. Whereas multiplex AD-MR families are rare, AD de novo mutations could explain numerous sporadic situations of non-specific MR and of autism with MR, in accordance with twin studies. Finally, we hypothesize that in those autistic subjects with mendelian MR, the XL-MR or AD-MR gene (G1) would pave the way for a second Mendelian factor (G2) responsible for autism symptoms.
同卵双胞胎自闭症症状的高度一致性与异卵双胞胎和/或非双胞胎兄弟姐妹相比，表明自闭症具有高度的遗传决定因素。这些结果根据家族研究和数学模型假设了多因素决定论。然而，迄今为止，连锁和关联或候选基因策略未能确定明确涉及的机制。智力迟钝（MR）已知常与自闭症相关。已经报道了仅一名突变患者患有自闭症和 MR 的 X 连锁 XLMR 家系：已经显示不同的 X 连锁 MR 基因参与其中（NLGN4、MECP2、OPHN1、ZNF674 和 FRAXA），这并不表明它们可以是“自闭症基因”。结节性硬化症研究和报道的许多常染色体缺失区域显示在 MR-自闭症患者中缺失，这表明几个常染色体显性（AD）基因也可能涉及 MR 伴自闭症。虽然多发性 AD-MR 家系很少见，但 AD 新生突变可以解释许多非特异性 MR 和 MR 伴自闭症的散发病例，这与双胞胎研究一致。最后，我们假设在那些具有孟德尔性 MR 的自闭症患者中，XL-MR 或 AD-MR 基因（G1）将为负责自闭症症状的第二个孟德尔因素（G2）铺平道路。
