Istituto Auxologico Italiano, IRCCS, Laboratory of Medical Cytogenetics and Molecular Genetics, 20145 Milan, Italy.
Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98100 Messina, Italy.
Genes (Basel). 2021 Apr 27;12(5):652. doi: 10.3390/genes12050652.
To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which , , , and are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only , and genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of and better define how the two contiguous genes, and , might contribute to the clinical phenotype.
迄今为止，仅有五名 8p23.2-pter 微缺失患者表现出轻度至中度认知障碍和/或发育迟缓、畸形和神经行为问题。2010 年，Wu 描述的最小微缺失提示了一个 2.1Mb 的关键区域 (CR)，其中包括几个基因，其中 、 、 、 和 是主要候选基因。在这里，我们介绍了另外七名 8p23.2-pter 微缺失患者，缺失大小从 71.79kb 到 4.55Mb 不等。对之前报道的五名患者和 Decipher 数据库中的九名患者进行了回顾，确认了 CR 与可变的临床表型之间的关联，这些表型的特征为智力残疾/发育迟缓，包括语言和言语延迟和/或运动障碍、行为异常、自闭症谱系障碍、畸形、小头症、手指/脚趾异常和癫痫。基因型分析有助于缩小 8p23.3 的候选区域，该区域仅包含 、 和 基因，这些基因解释了与 8p23.2-pter 微缺失相关的广泛临床表型的主要特征。与之前提出的 CR 相比，该区域更为局限。总的来说，我们的数据支持这样一种假设，即 是神经发育/行为表型的实际最强候选基因。需要更多的患者来验证 和 基因的致病性作用，并更好地定义两个相邻基因 和 如何共同导致临床表型。
