Sun Wenjie, Yan Hong, Sun Mengxin, Wang Jie, Li Kunxia
Pediatric Internal Medicine, Yantai Yuhuangding Hospital, No.20 Yuhuangding East Road, Zhifu District, Yantai City, Shandong, 264000, China.
BMC Pediatr. 2025 Jan 28;25(1):70. doi: 10.1186/s12887-025-05394-1.
Common clinical findings in patients with 19p13.3 duplication include intrauterine growth restriction, intellectual disability, developmental delay, microcephaly, and distinctive facial features. In this study, we report the case of a patient with 19p13.3 microduplication and novel clinical findings, specifically nephrotic syndrome.
A 4-year-old girl was admitted to our hospital in December 2020 with a fever and cough that had persisted for 3 days. A series of treatments, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were performed. Relevant literature was reviewed using the search terms "19p13.3" and "19p13.3 microduplication syndrome" in the China Knowledge Network, Wanfang Database, Weipu Journal Service Platform, and PubMed (date range: database establishment to September 2023). In addition to common symptoms, such as developmental delay, microcephaly, distinctive facial features, and congenital heart defects, the patient also had nephrotic syndrome, a previously unreported phenomenon. CMA results showed a 3.6 Mb fragment duplication (copy number: 3) in the chr19p13.3 region, containing 127 protein-coding genes (including CELF5, NFIC, SMIM24, PIAS4, ATCAY, MAP2K2, and ZBTB7A). WES revealed a filamin C mutation (p.Glu309Valfs × 11). The mutation status of the patient and her father was heterozygous, whereas the mutation was not detected in the mother.
Microduplication in the 19p13.3 region could be one of the genetic factors contributing to the observed clinical phenotypes. However, patients with developmental delay, microcephaly, distinctive facial features, congenital heart defects, and urogenital system disorders may exhibit these manifestations due to various genetic syndromes; therefore, simply considering the possibility of 19p13.3 microduplication syndrome based on these non-specific features is not sufficient. Further comprehensive evaluations, including CMA, should be conducted in conjunction with other genetic tests and detailed clinical examinations to accurately determine the underlying genetic causes.
19p13.3重复患者的常见临床特征包括宫内生长受限、智力残疾、发育迟缓、小头畸形和独特的面部特征。在本研究中，我们报告了一例患有19p13.3微重复且有新的临床发现的患者，具体为肾病综合征。
一名4岁女孩于2020年12月因持续3天的发热和咳嗽入住我院。进行了一系列治疗、染色体微阵列分析（CMA）和全外显子组测序（WES）。在中国知网、万方数据库、维普期刊服务平台和PubMed中使用检索词“19p13.3”和“19p13.3微重复综合征”（日期范围：数据库建立至2023年9月）对相关文献进行了综述。除了发育迟缓、小头畸形、独特的面部特征和先天性心脏缺陷等常见症状外，该患者还患有肾病综合征，这是一种以前未报道过的现象。CMA结果显示chr19p13.3区域有一个3.6 Mb的片段重复（拷贝数：3），包含127个蛋白质编码基因（包括CELF5、NFIC、SMIM24、PIAS4、ATCAY、MAP2K2和ZBTB7A）。WES揭示了细丝蛋白C突变（p.Glu309Valfs×11）。患者及其父亲的突变状态为杂合子，而母亲未检测到该突变。
19p13.3区域的微重复可能是导致观察到的临床表型的遗传因素之一。然而，发育迟缓、小头畸形、独特的面部特征、先天性心脏缺陷和泌尿生殖系统疾病患者可能由于各种遗传综合征而出现这些表现；因此，仅根据这些非特异性特征考虑19p13.3微重复综合征的可能性是不够的。应结合其他基因检测和详细的临床检查进行包括CMA在内的进一步综合评估，以准确确定潜在的遗传原因。
