Department of Pediatrics, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
CEN Case Rep. 2021 Aug;10(3):359-363. doi: 10.1007/s13730-021-00574-1. Epub 2021 Jan 21.
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.
双等位致病性变异在层粘连蛋白β2（LAMB2）基因中，该基因编码层粘连蛋白β2，与 Pierson 综合征有关，其特征为先天性肾病综合征迅速进展至终末期肾病、双侧小眼畸形的明显眼部发育不良以及神经发育缺陷。然而，LAMB2 相关疾病的表型谱比预期的更广泛，也有报道称存在表型较轻的病例，如孤立性先天性或婴儿期肾病综合征。我们报告了一例 LAMB2 相关肾脏疾病患者，其表现出极其轻微的表型。一名 5 岁女孩因尿分析筛查发现无症状蛋白尿和血尿就诊。她以前身体健康，无其他肾脏症状。血清白蛋白和肌酐水平正常。肾脏活检显示肾小球有轻微异常，偶尔有局灶性系膜增殖。电子显微镜检查显示肾小球基底膜无结构改变。使用下一代测序对足细胞相关基因进行靶向测序。结果发现先前报道的截短变异（c.5073_5076dupCCAG）和剪接位点变异（c.3797 + 5G > A）的双等位致病性变异在 LAMB2 基因中，患者被诊断为 LAMB2 相关肾脏疾病。有趣的是，先前报道的一例具有该剪接变异的病例也表现出异常轻微的表型。我们建议，如果肾小球基底膜无结构改变，临床医生应考虑将 LAMB2 相关肾炎作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查系统有助于诊断这些具有孤立性尿液异常的不典型病例。
