Systematic Review of Clinical Characteristics and Genotype-Phenotype Correlation in LAMB2-Associated Disease

Le résumé fourni par la source

Laminin subunit beta-2 (LAMB2) -associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome and ocular and neuromuscular symptoms. In recent years, however, the widespread use of next-generation sequencing has helped us discover a variety of phenotypes associated with this disease. Therefore, we conducted this systematic review. A literature search of patients with LAMB2 variants was conducted, and 110 patients were investigated, including 12 of our patients. For genotype-phenotype correlation analyses, the extracted data were investigated for pathogenic variant types, the severity of nephropathy, and extrarenal symptoms. Survival analyses were also performed for the onset age of end-stage kidney disease (ESKD). Among all patients, 81 (78%) presented with congenital nephrotic syndrome, and 52 (55%) developed ESKD within 12 months. The median age at ESKD onset was 6.0 months. Kidney survival analysis showed that patients with biallelic truncating variants had a significantly earlier progression to ESKD than those with other variants (median age 1.2 months vs. 60.0 months, p < 0.05). Although the laminin N-terminal domain is functionally important in laminin proteins, and variants in the laminin N-terminal domain are said to result in a severe kidney phenotype such as earlier onset age and worse prognosis, there were no significant differences in onset age of nephropathy and progression to ESKD between patients with non-truncating variants located in the laminin N-terminal domain and those with variants located outside this domain. This study revealed a diversity of LAMB2 -associated diseases, characteristics of LAMB2 nephropathy, and genotype-phenotype correlations.

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