PDF(Sci-hub)
Abstract：
Biallelic pathogenic variants in the laminin β2 (LAMB2) gene, which encodes laminin β2, are associated with Pierson syndrome characterized by a congenital nephrotic syndrome that rapidly progresses to end-stage renal disease, distinct ocular maldevelopment with bilateral microcoria, and neurodevelopmental deficits. However, the phenotypic spectrum of LAMB2-associated disorder is broader than expected, and cases with milder phenotypes such as isolated congenital or infantile nephrotic syndrome have also been reported. We report a patient with LAMB2-associated renal disorder showing an extremely mild phenotype. A 5-year-old girl presented with asymptomatic proteinuria and hematuria detected by urinalysis screening. She had been previously healthy without any additional renal symptoms. The serum albumin and creatinine levels were normal. Renal biopsy revealed minor glomerular abnormalities with occasional focal mesangial proliferation. Electron microscopy showed no structural changes in the glomerular basement membrane. Targeted sequencing of podocyte-related genes using next-generation sequencing was performed. As a result, previously reported biallelic pathogenic variants of the truncating variant (c.5073_5076dupCCAG) and a splice site variant (c.3797 + 5G > A) in the LAMB2 gene were detected, and the patient was diagnosed with LAMB2-associated renal disorder. Interestingly, a previously reported case with this splicing variant also showed an atypically mild phenotype. We suggest that clinicians should consider LAMB2-associated nephritis as an important differential diagnosis in children with asymptomatic proteinuria and microscopic hematuria if there is no structural change in the glomerular basement membrane. A comprehensive gene-screening system using next-generation sequencing is useful for diagnosing these atypical cases with isolated urine abnormalities.
摘要：
层粘连蛋白β2（LAMB2）基因的双等位基因致病变异，编码层粘连蛋白β2，与皮尔森综合征相关，其特征是先天性肾病综合征，迅速发展为终末期肾病，明显的眼部发育不良伴双侧微角膜，和神经发育缺陷。然而,LAMB2相关疾病的表型谱比预期的要宽，和轻度表型的病例，如孤立的先天性或婴儿肾病综合征也有报道。我们报告了一名患有LAMB2相关肾脏疾病的患者，表现出极其轻度的表型。一名5岁女孩通过尿液分析筛查发现无症状性蛋白尿和血尿。她以前很健康，没有任何其他肾脏症状。血清白蛋白和肌酐水平正常。肾活检显示肾小球轻度异常，偶有局灶性肾小球系膜增生。电子显微镜显示肾小球基底膜没有结构变化。使用下一代测序对足细胞相关基因进行靶向测序。因此,检测到LAMB2基因中截断变体（c.5073_5076dupCCAG）和剪接位点变体（c.37975G>A）的先前报道的双等位基因致病变体，患者被诊断为LAMB2相关肾脏疾病.有趣的是,先前报道的这种剪接变体的病例也显示出非典型的轻度表型。我们建议，如果肾小球基底膜没有结构变化，临床医生应将LAMB2相关性肾炎视为无症状蛋白尿和镜下血尿儿童的重要鉴别诊断。使用下一代测序的综合基因筛选系统可用于诊断这些具有孤立尿液异常的非典型病例。
