Wei Jieru, Zhao Gongping, Li Lijie, Liu Cuihua, Li Jitong
Department of Nephrology and Rheumatology, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
Children's Hospital Affiliated to Zhengzhou University, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Zhengzhou, 450018, China.
BMC Pediatr. 2025 Jun 9;25(1):468. doi: 10.1186/s12887-025-05810-6.
Variants in the LAGE3 gene can lead to Galloway-Mowat syndrome (GAMOS), a rare genetic disease. Currently, there have been a total of 6 reported cases worldwide, all occurring in children under the age of 3 years old. The main features of LAGE3 variants include early-onset nephrotic syndrome, microcephaly, developmental delay, and neurological abnormalities, with a poor prognosis. However, there are few reports on mild clinical manifestations and prognosis associated with LAGE3 variants.
Here, we report two brothers, aged 9 and 5 years old respectively, from a family, both presenting with nephrotic syndrome with different types of renal pathology. They both had a high-arched palate and were treated with steroids and tacrolimus, resulting in negative urine protein. Genetic sequencing revealed that both siblings carried a hemizygous variant in the LAGE3 gene: c.389T > G (p.V130G). However, neither of them exhibited the typical features of microcephaly, developmental delay, or neurological abnormalities associated with LAGE3 gene variants. Currently, both siblings have normal renal function and are being regularly followed up with a good prognosis.
This report is the first to document patients with LAGE3 variants who do not exhibit microcephaly, developmental delay, or neurological abnormalities. Additionally, it is the first case where proteinuria manifested at an older age and had a positive prognosis. The two siblings represent the 7th and 8th cases of children with LAGE3 variants, expanding the genotype and phenotype spectrum of LAGE3 variants, providing new insights for clinical diagnosis and risk assessment.
LAGE3基因变异可导致加洛韦-莫瓦特综合征（GAMOS），这是一种罕见的遗传病。目前，全球共报告了6例病例，均发生在3岁以下儿童。LAGE3基因变异的主要特征包括早发性肾病综合征、小头畸形、发育迟缓及神经异常，预后较差。然而，关于LAGE3基因变异相关的轻度临床表现及预后的报道较少。
在此，我们报告来自一个家庭的两兄弟，分别为9岁和5岁，均表现为肾病综合征且具有不同类型的肾脏病理改变。他们均有高拱腭，接受了类固醇和他克莫司治疗，尿蛋白转阴。基因测序显示，两兄弟均携带LAGE3基因的半合子变异：c.389T＞G（p.V130G）。然而，他们均未表现出与LAGE3基因变异相关的小头畸形、发育迟缓或神经异常的典型特征。目前，两兄弟肾功能正常，正在定期随访，预后良好。
本报告首次记录了未表现出小头畸形、发育迟缓或神经异常的LAGE3基因变异患者。此外，这也是首例蛋白尿在较大年龄出现且预后良好的病例。这两兄弟代表了第7和第8例LAGE3基因变异儿童病例，扩展了LAGE3基因变异的基因型和表型谱，为临床诊断和风险评估提供了新的见解。
