Türkyılmaz Ayberk, Sağer Safiye Güneş, Caliskan Emine, Akçay Merve, Demir Oğuzhan, Baytar Baran, Akın Yasemin
Department of Medical Genetics, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
Department of Pediatric Neurology, Kartal Dr. Lütfi Kırdar City Hospital, Health Science University İstanbul, İstanbul, Turkey.
Mol Syndromol. 2025 Apr;16(2):99-114. doi: 10.1159/000540599. Epub 2024 Aug 23.
Copy number variation (CNV) is the difference in the sequence of genomic segments, which can vary from one kilobase to several megabases. Certain CNVs have been linked to various human disorders, such as intellectual disability, multiple congenital anomalies, autism spectrum disorders, neurodegenerative and neuropsychiatric conditions, and cancer. The present study aims to classify brain magnetic resonance imaging (MRI) findings, describe neurological manifestations, and discuss the findings within the context of genotype-phenotype correlations in a cohort of patients with recurrent and nonrecurrent CNVs.
A total of 21 patients with pathogenic CNV detected using microarray analysis were included in the study.
Analysis of the clinical findings of the patient cohort showed that 16 (76%) had microcephaly, 14 had epilepsy (66%), 20 had facial dysmorphism (95%), and all had developmental delay (100%). Novel brain MRI findings were detected in six (6/13, 46%) patients with recurrent CNV and five (5/8, 63%) patients with nonrecurrent CNV.
CNV-related disorders should be considered in the differential diagnosis of patients with brain MRI findings suspicious for metabolic disorders. Brain MRI differences in patients with the same chromosomal deletion can be explained by the second-hit hypothesis. Additional single nucleotide variations and epigenetic factors in these cases may have led to the involvement of different regions of the brain. Revealing the phenotypic and genotypic characteristics of cases in rare disorders will contribute to the widespread use of precision medicine and genetic treatment approaches in the near future.
拷贝数变异（CNV）是基因组片段序列的差异，其长度可从一千碱基到几兆碱基不等。某些CNV与多种人类疾病相关，如智力残疾、多发性先天性异常、自闭症谱系障碍、神经退行性和神经精神疾病以及癌症。本研究旨在对一组患有复发性和非复发性CNV的患者的脑磁共振成像（MRI）结果进行分类，描述神经学表现，并在基因型-表型相关性的背景下讨论这些结果。
本研究共纳入21例经微阵列分析检测出致病性CNV的患者。
对患者队列的临床结果分析显示，16例（76%）有小头畸形，14例有癫痫（66%），20例有面部畸形（95%），所有患者均有发育迟缓（100%）。在6例（6/13，46%）复发性CNV患者和5例（5/8，63%）非复发性CNV患者中检测到新的脑MRI结果。
对于脑MRI结果疑似代谢紊乱的患者，鉴别诊断时应考虑CNV相关疾病。相同染色体缺失患者的脑MRI差异可用二次打击假说来解释。这些病例中的其他单核苷酸变异和表观遗传因素可能导致了大脑不同区域的受累。揭示罕见疾病病例的表型和基因型特征将有助于在不久的将来广泛应用精准医学和基因治疗方法。
