Laboratory of Medical Genetics, Medical School, National and Kapodistrian University of Athens, St. Sophia Children's Hospital, 11527 Athens, Greece.
University Research Institute for the Study and Treatment of Genetic and Malignant Disorders of Childhood, 11527 Athens, Greece.
Genes (Basel). 2024 Aug 10;15(8):1053. doi: 10.3390/genes15081053.
The human 16p11.2 chromosomal region is rich in segmental duplications which mediate the formation of recurrent CNVs. CNVs affecting the 16p11.2 region are associated with an increased risk for developing neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability (ID), as well as abnormal body weight and head circumference and dysmorphic features, with marked phenotypic variability and reduced penetrance. CNVs affecting the 16p11.2 region mainly affect a distal interval of ~220 Kb, between Breakpoints 2 and 3 (BP2-BP3), and a proximal interval of ~593 Kb (BP4-BP5). Here, we report on 15 patients with recurrent 16p11.2 rearrangements that were identified among a cohort of 1600 patients (0.9%) with neurodevelopmental disorders. A total of 13 deletions and two duplications were identified, of which eight deletions included the proximal 16p11.2 region (BP4-BP5) and five included the distal 16p11.2 region (BP2-BP3). Of the two duplications that were identified, one affected the proximal and one the distal 16p11.2 region; however, both patients had additional CNVs contributing to phenotypic severity. The features observed and their severity varied greatly, even between patients within the same family. This article aims to further delineate the clinical spectrum of patients with 16p11.2 recurrent rearrangements in order to aid the counselling of patients and their families.
人类 16p11.2 染色体区域富含片段重复序列，这些重复序列介导了反复出现的 CNV 的形成。影响 16p11.2 区域的 CNV 会增加患神经精神疾病的风险，包括自闭症谱系障碍（ASD）、精神分裂症和智力障碍（ID），以及异常的体重和头围和畸形特征，具有明显的表型变异性和降低的外显率。影响 16p11.2 区域的 CNV 主要影响约 220 Kb 的远端间隔，在断点 2 和 3 之间（BP2-BP3），以及约 593 Kb 的近端间隔（BP4-BP5）。在这里，我们报告了在 1600 名神经发育障碍患者（0.9%）队列中发现的 15 例反复出现的 16p11.2 重排患者。共发现 13 个缺失和 2 个重复，其中 8 个缺失包括近端 16p11.2 区域（BP4-BP5），5 个缺失包括远端 16p11.2 区域（BP2-BP3）。鉴定出的两个重复之一影响近端，另一个影响远端 16p11.2 区域；然而，这两名患者都有其他的 CNV 导致表型严重程度增加。观察到的特征及其严重程度差异很大，即使是在同一家庭的患者之间也是如此。本文旨在进一步描绘 16p11.2 反复重排患者的临床谱，以帮助患者及其家属进行咨询。
