Center for Human Genetics, Clinical Genetics, University of Leuven, Leuven, Belgium.
Clin Genet. 2010 Apr;77(4):389-94. doi: 10.1111/j.1399-0004.2009.01318.x. Epub 2009 Dec 10.
We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigate the causal relationship of the duplication to the autism phenotype. We conclude that the 1q42.2 microduplication probably confers susceptibility to autism in the current family. This study is a typical illustration of the difficult interpretation of causality of a very rare variant in neuropsychiatric disease and the challenge of genetic counselling in a particular family.
我们描述了在两名自闭症和轻度智力障碍的兄弟中发现的 1q42.2 号染色体上的一个 2.07Mb 微重复的鉴定和划定。由于这个重复在 1577 名比利时人中不存在，我们认为这是一种极其罕见的变体，有可能进一步深入了解自闭症的遗传学。该重复包含七个基因，包括 DISC1 基因，这是一个有趣的候选基因，与精神分裂症、双相情感障碍、自闭症和阿斯伯格综合征有关。在本报告中，我们描述了为研究该重复与自闭症表型的因果关系而进行的其他分析。我们的结论是，1q42.2 微重复可能导致当前家庭的自闭症易感性。这项研究典型地说明了在神经精神疾病中非常罕见的变体的因果关系的解释非常困难，以及在特定家庭中进行遗传咨询的挑战。
