Department of Pediatric Nephrology, Institute of Kidney Diseases and Research Centre, Gujarat University of Transplantation Sciences, Ahmedabad, India.
Department of Nephrology, Institute of Kidney Diseases and Research Centre, Gujarat University of Transplantation Sciences, Ahmedabad, India.
BMC Nephrol. 2023 Jul 18;24(1):212. doi: 10.1186/s12882-023-03240-z.
Kidney diseases with genetic etiology in children present with an overlapping spectrum of manifestations. We aimed to analyze the clinical utility of genetic testing in the diagnosis and management of suspected genetic kidney diseases in children.
In this retrospective study, children ≤ 18 years in whom a genetic test was ordered were included. Clinical indications for genetic testing were categorized as Glomerular diseases, nephrolithiasis and/or nephrocalcinoses, tubulopathies, cystic kidney diseases, congenital abnormality of kidney and urinary tract, chronic kidney disease of unknown aetiology and others. Clinical exome sequencing was the test of choice. Other genetic tests ordered were sanger sequencing, gene panel, multiplex ligation-dependent probe amplification and karyotyping. The pathogenicity of the genetic variant was interpreted as per the American College of Medical Genetics classification.
A total of 86 samples were sent for genetic testing from 76 index children, 8 parents and 2 fetuses. A total of 74 variants were reported in 47 genes. Out of 74 variants, 42 were missense, 9 nonsense, 12 frameshifts, 1 indel, 5 affected the splicing regions and 5 were copy number variants. Thirty-two were homozygous, 36 heterozygous and 6 were hemizygous variants. Twenty-four children (31.6%) had pathogenic and 11 (14.5%) had likely pathogenic variants. Twenty-four children (31.6%) had variants of uncertain significance. No variants were reported in 17 children (22.3%). A genetic diagnosis was made in 35 children with an overall yield of 46%. The diagnostic yield was 29.4% for glomerular diseases, 53.8% for tubular disorders, 81% for nephrolithiasis and/or nephrocalcinoses, 60% for cystic kidney diseases and 50% for chronic kidney disease of unknown etiology. Genetic testing made a new diagnosis or changed the diagnosis in 15 children (19.7%).
Nearly half (46%) of the children tested for a genetic disease had a genetic diagnosis. Genetic testing confirmed the clinical diagnoses, changed the clinical diagnoses or made a new diagnosis which helped in personalized management.
儿童遗传性肾脏疾病表现出重叠的临床表现谱。本研究旨在分析基因检测在儿童疑似遗传性肾脏疾病的诊断和管理中的临床应用价值。
本回顾性研究纳入了接受基因检测的≤18 岁儿童。基因检测的临床指征分为肾小球疾病、肾结石和/或肾钙质沉着症、肾小管疾病、囊性肾脏疾病、肾和尿路先天性异常、原因不明的慢性肾脏疾病和其他疾病。临床外显子组测序是首选的检测方法。其他基因检测包括桑格测序、基因panel、多重连接依赖性探针扩增和核型分析。根据美国医学遗传学学院的分类方法对遗传变异的致病性进行解读。
共 76 名索引儿童、8 名父母和 2 名胎儿的 86 个样本送检进行基因检测。在 47 个基因中共报告了 74 个变异。74 个变异中，42 个为错义变异，9 个为无义变异，12 个为移码变异，1 个为插入缺失变异，5 个影响剪接区，5 个为拷贝数变异。32 个为纯合变异，36 个为杂合变异，6 个为半合子变异。24 名儿童（31.6%）存在致病性或可能致病性变异，24 名儿童（31.6%）存在意义不明的变异。17 名儿童（22.3%）未报告变异。35 名儿童（46%）做出了基因诊断。肾小球疾病的诊断率为 29.4%，肾小管疾病为 53.8%，肾结石和/或肾钙质沉着症为 81%，囊性肾脏疾病为 60%，原因不明的慢性肾脏疾病为 50%。基因检测在 15 名儿童（19.7%）中做出了新的诊断或改变了诊断。
近一半（46%）接受遗传性疾病基因检测的儿童做出了基因诊断。基因检测证实了临床诊断、改变了临床诊断或做出了新的诊断，有助于进行个体化管理。
