Abstract: PO1654
LAMA5 Gene Mutations in Japanese Cases with Infantile Nephrotic Syndrome
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Nagano, China, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Nozu, Kandai, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Ishiko, Shinya, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Aoto, Yuya, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Sakakibara, Nana, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Horinouchi, Tomoko, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Yamamura, Tomohiko, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Ninchoji, Takeshi, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Iijima, Kazumoto, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Background
Steroid resistant nephrotic syndrome (SRNS) have high risks to progress to end stage renal disease. Mutations in genes encoding podocyte-associated proteins have been implicated in about 30% of SRNS cases in children. Recently, LAMA5 gene mutation have been identified in patients with nephrotic syndrome. The LAMA5 gene encodes laminin α5, an essential component of the glomerular basement membrane. Here, we report the three cases with LAMA5 gene mutations.
Methods
We conducted comprehensive gene screening of Japanese patients with severe proteinuria. Using targeted next-generation sequencing, 60 podocyte-related genes were screened in 326 unrelated patients with proteinuria.
Results
LAMA5 gene variants were detected in two families. The patient 1 and 2 were siblings. They presented with proteinuria at ages three months and four months, respectively. They were subsequently found to have compound heterozygous mutation for LAMA5 gene (NM_005560). One was nonsense mutation (c.9232C>T, p.Arg3078Ter), and the other was splice site mutation (c.1282+1G>A). The patient 3 presented with proteinuria at 6 months old. She had congenital cataract and hypoplastic kidney. Her renal pathology showed remarkable irregular form of glomerular basement membrane. She was subsequently found to have compound heterozygous mutation for LAMA5 gene: c.8185C>T (p.Arg2720Ter), c.1282+1G>A. We performed immunofluorescence analysis of laminin α5 and her renal pathology showed completely negative staining pattern.
Conclusion
Our cases show clinical and pathological findings in a very rare disease of LAMA5 related nephropathy. Patient 3 showed more severe phenotype compare to patient 1 and 2. We speculate the reason for this difference is the position of the variants, i.e. Patient 3 lacks laminin G-like domains that is the major cell-adhesive sites of laminin. LAMA5 gene mutation screening should be performed in congenital/infantile nephrotic syndrome cases. Further investigation for this disease entity should be notified to all pediatricians.