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| Year : 2021 | Volume
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| Issue : 5 | Page : 1479-1481 |
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| Heterozygous laminin β2 mutation in C3 glomerulopathy |
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Manish R Balwani1, Amit S Pasari1, Amol R Bhawane1, Priyanka R Tolani2
1 Department of Nephrology, Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
2 Department of Medicine, NKP Salve Institute of Medical Sciences, Nagpur, Maharashtra, India
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| Date of Web Publication | 4-May-2022 |
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 Abstract | | |
C3 glomerulopathy is usually seen with the presence of C3 nephritic factor, homozygous or heterozygous mutations in the regulatory complement proteins factor H, factor I, or C3. We describe the presence of heterozygous laminin β2 mutation in a patient of C3 glomerulonephritis with ocular and central nervous system involvement, the significance of which is unknown.
How to cite this article:
Balwani MR, Pasari AS, Bhawane AR, Tolani PR. Heterozygous laminin β2 mutation in C3 glomerulopathy. Saudi J Kidney Dis Transpl 2021;32:1479-81 |
How to cite this URL:
Balwani MR, Pasari AS, Bhawane AR, Tolani PR. Heterozygous laminin β2 mutation in C3 glomerulopathy. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1479-81. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1479/344772 |
| Introduction | |  |
Mutations in the laminin β2 (LAMB2) gene are described with Pierson syndrome consisting of congenital nephrotic syndrome (NS) with rapid progression to end-stage renal disease, ocular abnormalities and neurodevelopmental delay.[1] Mild phenotypes have also been described with LAMB mutation.[2] Here, we describe the LAMB2 mutation in a patient of C3 glomerulopathy, the significance of which is unknown.
| Case Report | | |
A 31-year-old patient who was a diagnosed case of renal biopsy proven C3 glomerulopathy came with features suggestive of NS. First renal biopsy without electron microscopic examination was performed for NS in 2014. Renal biopsy in 2014 was suggestive of membrano-proliferative glomerulonephritis with dominant C3 staining. In 2014, he was treated on the lines of post-infective glomerulonephritis. He received short course of steroids for three months. Afterward, he had persistent proteinuria and was kept on angiotension-converting enzyme inhibitors (ACEI). Second renal biopsy was performed in 2017 for persistent features of nephrotic syndrome. This biopsy showed membranoproliferative pattern glomerulonephritis with predominantly C3 staining on immuno-fluorescence. Electron microscopy revealed electron dense deposits in mesangial, sub-endothelial and subepithelial region. Thus, a diagnosis of C3 glomerulonephritis was made for which he received steroids and mycophenolate mofetil for one year. He never achieved remission with treatment. He stopped all medicines on his own after one year of treatment and shifted to alternative herbal medicines. In 2020, he consulted us for persistent features of NS where his past records were reviewed and patient was explained regarding the nature of disease. During these five years, he had persistent low serum complement C3 levels with normal C4 levels. During hospitalization, he was given symptomatic treatment in the form of diuretics, albumin supplementation, ACEI, fluid restriction, and other supportive measures. Ophthalmic evaluation was performed which showed drusen. He had seizures during hospitalization. Structural cause was ruled out with MRI imaging, all electrolyte and biochemical reports were normal. Electroencephalogram was suggestive of slow delta waves and there was no epileptiform abnormality. Genetic analysis was performed which showed the presence of compound heterozygous variants in the LAMB2 gene. A missense variation in exon 17 of the LAMB2 gene (chr3:g.49126015C>T; Depth: 75x) that resulted in the amino acid substitution of Threonine for Alanine at codon 766 (p.Ala766Thr; ENST00000305544.9) was detected. Another missense variation in exon 17 of the LAMB2 gene (chr3:g.49126075G>A; Depth: 98x) that resulted in the amino acid substitution of Cysteine for Arginine at codon 746 (p.Arg746Cys; ENST00000305544.9) was detected. Genetic analysis of parents was not performed due to financial constraints. Here we report widening spectrum of LAMB 2 gene related renal disorders where we found C3 glomerulopathy along with drusens in eye and generalized tonic-clonic seizures.
The authors obtained all appropriate consent forms from the patient for the publication of this case report.
| Discussion | | |
LAMB2 mutations were initially described with severe presentation of Pierson syndrome.[1] Few children with Pierson syndrome who could survive infancy exhibited advanced neuro-developmental delay and blindness.[3] There is association of truncating LAMB2 mutations with complete lack of laminin b2 in Pierson phenotype.[3],[4] In few cases, missense changes in LAMB2 demonstrated less severe hypomorphic alleles. They are associated with higher mean age at onset of renal disease and with absence of neurologic abnormalities.[2],[5]
C3 glomerulopathy is a disease due to dysregulation in alternative complement pathway.[6] It can be due to dysregulation in factors that regulate the complement functions like complement factor H, complement factor H-related proteins, complement factor I, membrane cofactor protein, and complement factor B.[6],[7] Here, in our case, we performed genetic analysis to look for mutation in complement pathway proteins. However, it showed missense variations in LAMB2. Till date, no literature describes any association or simultaneous presence of C3 glomerulopathy and LAMB2 mutation. It may be mere coinicidence of presence of LAMB2 mutation in C3 glomerulonephritis or there may be association which cannot be commented upon right now in view of lack of evidence. These LAMB2 variations seen in our case are likely to be compound heterozygous variants of uncertain significance. Author is of opinion that whole spectrum of renal, ophthalmic and central nervous system involvement in our case may be mild phenotypic presentation of missense mutation of LAMB 2 gene. It is important to note that genotype alone does not explain the full range of clinical phenotype presentation as many unrecognized modifiers exist.
| Conclusions | | |
Our case report widens the spectrum of LAMB2-associated renal disorders to C3 glomerulopathy with ocular drusens and generalized tonic-clonic seizures in adult male patient. Relevance of such missense mutation in C3 GN is unknown and further studies are warranted to know or reject the causal association.
Conflict of interest: None declared.
| References | | |
| 1. | Pierson M, Cordier J, Hervouuet F, Rauber G. An unusual congenital and familial congenital malformative combination involving the eye and kidney. J Genet Hum 1963;12:184-213.  |
| 2. | Hasselbacher K, Wiggins RC, Matejas V, et al. Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int 2006;70:1008-12. |
| 3. | Zenker M, Aigner T, Wendler O, et al. Human laminin β2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 2004;13: 2625-32. |
| 4. | Zenker M, Pierson M, Jonveaux P, Reis A. Demonstration of two novel LAMB2 mutations in the original Pierson syndrome family reported 42 years ago. Am J Med Genet A 2005;138:73-4. |
| 5. | Sethi S. Etiology-based diagnostic approach to proliferative glomerulonephritis. Am J Kidney Dis 2014;63:561-6. |
| 6. | Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: A key system for immune surveillance and homeostasis. Nat Immunol 2010;11:785-97. |
| 7. | Thurman JM. Complement in kidney disease: Core curriculum 2015. Am J Kidney Dis 2015; 65:156-68. |
Correspondence Address:
Manish R Balwani
Department of Nephrology, Jawaharlal Nehru Medical College, Sawangi,Wardha, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1319-2442.344772
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