An extremely mild clinical course in a case with LAMB2-associated nephritis diagnosed with next-generation sequencing
- 21 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in CEN Case Reports
- Vol. 10 (3), 359-363
- https://doi.org/10.1007/s13730-021-00574-1
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.Keywords
This publication has 14 references indexed in Scilit:
- LAMB2 mutation with different phenotypes in ChinaClinical Nephrology, 2017
- Pierson syndrome in an adolescent girl with nephrotic range proteinuria but a normal GFRPediatric Nephrology, 2012
- Mutations in the human laminin β2 (LAMB2) gene and the associated phenotypic spectrumaHuman Mutation, 2010
- Variable phenotype of Pierson syndromePediatric Nephrology, 2008
- A milder variant of Pierson syndromePediatric Nephrology, 2007
- Nephrotic Syndrome in the First Year of Life: Two Thirds of Cases Are Caused by Mutations in 4 Genes (NPHS1, NPHS2, WT1, and LAMB2)PEDIATRICS, 2007
- Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disordersKidney International, 2006
- Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: An autosomal recessive syndromeAmerican Journal of Medical Genetics Part A, 2004
- Renal basement membrane componentsKidney International, 1999
- [AN UNUSUAL CONGENITAL AND FAMILIAL CONGENITAL MALFORMATIVE COMBINATION INVOLVING THE EYE AND KIDNEY].1963