Männik Katrin, Parkel Sven, Palta Priit, Zilina Olga, Puusepp Helen, Esko Tõnu, Mägi Reedik, Nõukas Margit, Veidenberg Andres, Nelis Mari, Metspalu Andres, Remm Maido, Ounap Katrin, Kurg Ants
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Eur J Med Genet. 2011 Mar-Apr;54(2):136-43. doi: 10.1016/j.ejmg.2010.11.005. Epub 2010 Nov 26.
The increasing use of whole-genome array screening has revealed the important role of DNA copy-number variations in the pathogenesis of neurodevelopmental disorders and several recurrent genomic disorders have been defined during recent years. However, some variants considered to be pathogenic have also been observed in phenotypically normal individuals. This underlines the importance of further characterization of genomic variants with potentially variable expressivity in both patient and general population cohorts to clarify their phenotypic consequence. In this study whole-genome SNP arrays were used to investigate genomic rearrangements in 77 Estonian families with idiopathic mental retardation. In addition to this family-based approach, phenotype and genotype data from a cohort of 1000 individuals in the general population were used for accurate interpretation of aberrations found in mental retardation patients. Relevant structural aberrations were detected in 18 of the families analyzed (23%). Fifteen of those were in genomic regions where clinical significance has previously been established. In 3 families, 4 novel aberrations associated with intellectual disability were detected in chromosome regions 2p25.1-p24.3, 3p12.1-p11.2, 7p21.2-p21.1 and Xq28. Carriers of imbalances in 15q13.3, 16p11.2 and Xp22.31 were identified among reference individuals, affirming the variable phenotypic consequence of rare variants in some genomic regions considered as pathogenic.
全基因组阵列筛查的使用日益增加，揭示了DNA拷贝数变异在神经发育障碍发病机制中的重要作用，并且近年来已经定义了几种复发性基因组疾病。然而，在表型正常的个体中也观察到了一些被认为是致病性的变异。这凸显了在患者和普通人群队列中进一步表征具有潜在可变表达性的基因组变异以阐明其表型后果的重要性。在本研究中，使用全基因组SNP阵列来研究77个患有特发性智力障碍的爱沙尼亚家庭中的基因组重排。除了这种基于家庭的方法外，还使用了来自普通人群中1000名个体队列的表型和基因型数据，以准确解释在智力障碍患者中发现的畸变。在所分析的18个家庭（23%）中检测到了相关的结构畸变。其中15个位于先前已确定临床意义的基因组区域。在3个家庭中，在染色体区域2p25.1-p24.3、3p12.1-p11.2、7p21.2-p21.1和Xq28中检测到4种与智力残疾相关的新型畸变。在参考个体中鉴定出了15q13.3、16p11.2和Xp22.31失衡的携带者，证实了在一些被认为是致病性的基因组区域中罕见变异的可变表型后果。
