CLCN5基因存在无义致病性变异的I型丹特病的产前诊断：病例报告
Prenatal diagnosis of dent disease type I with a nonsense pathogenic variant in CLCN5: a case study.
作者信息
Zhu Ruijue, Zhu Mingming, Wang Boye, Chen Enen, Cai Danlei, Yang Yinghong, Liang Yi, Su Chuqi, Wang Ding, Sun Xiaofang, Huang Linhuan, Xie Yingjun
机构信息
Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, No. 63 of Duobao Road, 510150, Guangzhou, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, 511436, Guangzhou, Guangdong, China.
出版信息
BMC Med Genomics. 2024 Jan 24;17(1):34. doi: 10.1186/s12920-024-01809-7.
INTRODUCTION
Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians.
METHODS
A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis.
RESULTS
No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features.
CONCLUSION
This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.
引言
I型丹特病是一种罕见的X连锁隐性肾小管疾病，由CLCN5基因的致病变异引起。由于I型丹特病的罕见性及其表型的多样性，其临床诊断较为复杂，给临床医生带来了挑战。
方法
本研究纳入了一名36岁有不良生育史的孕妇所生的一名胎儿和一名儿童。孕妇在孕12周时接受羊膜腔穿刺术进行产前诊断。采用染色体微阵列（CMA）分析和全外显子组测序（WES）来研究染色体拷贝数和单基因变异。进行文献检索和数据分析以收集基因型和表型进行分析。
结果
通过核型分析和家族性CMA分析，在整个家族中未检测到染色体异常或拷贝数变异。WES在X染色体的CLCN5基因中鉴定出一个无义致病变异，c.1942 C>T（外显子11，NM_000084），该变异遗传自其母亲，其母亲表现出正常的临床特征。
结论
本研究表明，患有低分子量蛋白尿和高钙尿症的儿童应及时进行基因检测以排除丹特病。
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