Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea.
Int J Mol Sci. 2023 Dec 23;25(1):253. doi: 10.3390/ijms25010253.
16p11.2 copy number variations (CNVs) are increasingly recognized as one of the most frequent genomic disorders, and the 16p11.2 microdeletion exhibits broad phenotypic variability and a diverse clinical phenotype. We describe the neurodevelopmental course and discordant clinical phenotypes observed within and between individuals with identical 16p11.2 microdeletions. An analysis with the CytoScan Dx Assay was conducted on a GeneChip System 3000Dx, and the sample signals were then compared to a reference set using the Chromosome Analysis Suite software version 3.1. Ten patients from six separate families were identified with 16p11.2 microdeletions. Nine breakpoints (BPs) 4-5 and one BP2-5 of the 16p11.2 microdeletion were identified. All patients with 16p11.2 microdeletions exhibited developmental delay and/or intellectual disability. Sixty percent of patients presented with neonatal hypotonia, but muscle weakness improved with age. Benign infantile epilepsy manifested between the ages of 7-10 months (a median of 8 months) in six patients (60%). Vertebral dysplasia was observed in two patients (20%), and mild scoliosis was noted in three patients. Sixty percent of patients were overweight. We present six unrelated Korean families, among which identical 16p11.2 microdeletions resulted in diverse developmental trajectories and discordant phenotypes. The clinical variability and incomplete penetrance observed in individuals with 16p11.2 microdeletions remain unclear, posing challenges to accurate clinical interpretation and diagnosis.
16p11.2 拷贝数变异 (CNVs) 越来越被认为是最常见的基因组疾病之一,16p11.2 微缺失表现出广泛的表型变异性和多样化的临床表型。我们描述了具有相同 16p11.2 微缺失的个体内部和之间观察到的神经发育过程和不一致的临床表型。使用 CytoScan Dx 分析在 GeneChip System 3000Dx 上进行,然后使用 Chromosome Analysis Suite 软件版本 3.1 将样本信号与参考集进行比较。从六个不同的家庭中确定了 10 名患有 16p11.2 微缺失的患者。确定了 16p11.2 微缺失的 9 个断点 (BP) 4-5 和一个 BP2-5。所有患有 16p11.2 微缺失的患者均表现出发育迟缓或智力残疾。60%的患者出现新生儿低张力,但肌肉无力随年龄增长而改善。6 名患者(60%)在 7-10 个月(中位数为 8 个月)出现良性婴儿癫痫。两名患者(20%)出现椎骨发育不良,三名患者出现轻度脊柱侧凸。60%的患者超重。我们介绍了六个不相关的韩国家庭,其中相同的 16p11.2 微缺失导致了不同的发育轨迹和不一致的表型。16p11.2 微缺失个体的临床变异性和不完全外显率仍不清楚,这对准确的临床解释和诊断构成挑战。