Buianova Anastasiia A, Lashkova Yulia S, Kulichenko Tatiana V, Kuznetsov Ivan S, Ivanov Artem A, Parshina Olga P, Suchalko Oleg N, Vakhlyarskaya Svetlana S, Korostin Dmitriy O
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 1, bld. 1, Ostrovityanova St., Moscow, 117513, Russia.
Russian Children's Clinical Hospital, 117 Leninsky Prospect, Moscow, 119571, Russia.
Neurol Res Pract. 2025 Apr 7;7(1):22. doi: 10.1186/s42466-025-00378-z.
Congenital anomalies and neurodevelopmental disorders are complex conditions often requiring comprehensive diagnostic approaches. Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has greatly improved the detection of pathogenic variants, including copy number variations (CNVs), which account for up to 35% of genetic causes in neurological patients. Combining CNV and single nucleotide variant (SNV) analysis through WES enhances diagnostic accuracy, especially in cases with unclassified congenital anomalies.
This study reports a 14-year-old male patient with multiple congenital anomalies, including hypospadias, complete cleft palate, and recurrent pneumonia. His clinical presentation includes significant physical and intellectual developmental delays, autism-like symptoms, and spastic diplegia. Whole-exome sequencing (WES) was performed due to these complex symptoms, revealing a novel heterozygous deletion on chromosome 10q24.31-q24.33. Laboratory findings indicated agammaglobulinemia, leading to prophylactic antibiotic therapy and immunoglobulin replacement. Additional imaging studies showed cystic malformation of the middle lobe of the right lung, sliding hiatal hernia with prolapse of the gastric mucosa, and brain anomalies consistent with Joubert syndrome.
This case underscores the importance of genetic analysis in understanding the etiology of congenital anomalies and neurodevelopmental disorders, providing critical insights into the molecular mechanisms driving complex phenotypes. The identified chromosomal deletion contributes to the existing literature on genomic imbalances associated with similar phenotypes.
先天性异常和神经发育障碍是复杂的病症，通常需要综合诊断方法。新一代测序（NGS），尤其是全外显子组测序（WES），极大地提高了对致病变异的检测能力，包括拷贝数变异（CNV），其在神经系统疾病患者的遗传病因中占比高达35%。通过WES将CNV和单核苷酸变异（SNV）分析相结合可提高诊断准确性，特别是在未分类的先天性异常病例中。
本研究报告了一名14岁男性患者，患有多种先天性异常，包括尿道下裂、完全性腭裂和反复肺炎。他的临床表现包括明显的身体和智力发育迟缓、自闭症样症状和痉挛性双侧瘫。由于这些复杂症状进行了全外显子组测序（WES），结果显示在染色体10q24.31-q24.33上存在一个新的杂合缺失。实验室检查结果表明存在无丙种球蛋白血症，导致采取预防性抗生素治疗和免疫球蛋白替代治疗。其他影像学检查显示右肺中叶囊性畸形、滑动性食管裂孔疝伴胃黏膜脱垂以及与Joubert综合征一致的脑部异常。
该病例强调了基因分析在理解先天性异常和神经发育障碍病因方面的重要性，为驱动复杂表型的分子机制提供了关键见解。所鉴定的染色体缺失为与相似表型相关的基因组失衡的现有文献增添了内容。
