An extremely mild clinical course in a case with LAMB2-associated nephritis diagnosed with next-generation sequencing.
An extremely mild clinical course in a case with LAMB2-associated nephritis diagnosed with next-generation sequencing.
复制标题
通过新一代测序诊断出 LAMB2 相关肾炎病例的临床病程极其轻微。
DOI：
10.1007/s13730-021-00574-1
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发表时间：
2021
期刊：
影响因子：
1
通讯作者：
Ohtomo Y.
中科院分区：
文献类型：
--
作者：
Sakuraya K;Nozu K;Murakami H;Nagano C;Horinouchi T;Fujinaga S;Iijima K;Ohtomo Y.
编码层粘连蛋白β2的层粘连蛋白β2（LAMB2）基因的双等位基因致病性变体与皮尔逊综合征相关，其特征为先天性肾病综合征，可迅速进展为终末期肾病、明显的眼部发育不良伴双侧小瞳孔和神经发育缺陷。然而，LAMB2相关疾病的表型谱比预期的要广，并且也有报告具有较轻表型的病例，如孤立的先天性或婴儿肾病综合征。我们报告一个病人与LAMB2相关的肾脏疾病显示一个非常轻微的表型。一个5岁的女孩，表现为无症状的蛋白尿和血尿。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微异常，偶见局灶性系膜增生。电子显微镜检查显示肾小球基底膜无结构变化。使用下一代测序进行足细胞相关基因的靶向测序。结果，在LAMB2基因中检测到了先前报道的截短变异体（c.5073_5076dupCCAG）和剪接位点变异体（c.3797 + 5G > A）的双等位基因致病变异体，并诊断为LAMB2相关肾病。有趣的是，以前报道的这种剪接变异体的病例也显示出轻微的病理表型。我们建议临床医生应将LAMB 2相关性肾炎作为无症状性蛋白尿和镜下血尿患儿的重要鉴别诊断，如果肾小球基底膜无结构改变。使用下一代测序的综合基因筛查系统可用于诊断这些具有孤立尿液异常的非典型病例。
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 ofLAMB2-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 withLAMB2-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 theLAMB2gene were detected, and the patient was diagnosed withLAMB2-associated renal disorder. Interestingly, a previously reported case with this splicing variant also showed an atypically mild phenotype. We suggest that clinicians should considerLAMB2-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.