Abstract
A two-and-a-half-month-old female infant presented with generalized edema for 10 days. At presentation, she had periorbital puffiness, moderate ascites, and pedal edema. Laboratory investigations revealed serum albumin 1.3 g/dL, spot urine protein to creatinine ratio (Up:Uc) 20.87 mg/mg, total cholesterol 380 mg/dL, and serum creatinine 0.31 mg/dL. Exome sequencing revealed compound heterozygous variants in LAMA5 gene (NM_005560.6). There was a heterozygous likely pathogenic missense variant in exon 2: LAMA5: c.385C > A (depth 195 ×) and another heterozygous pathogenic variant in exon 31: LAMA5: c.3932_3936dup; parental segregation by Sanger sequencing proved that the variants were in trans. Kidney biopsy showed diffuse mesangial sclerosis (DMS). Our case adds LAMA5 gene to the constellation of genes causing DMS, in addition to the classically described WT1, LAMB2, and PLCE1 genes and to the list of genes causing congenital nephrotic syndrome (CNS).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Joshi A, Sinha A, Sharma A, Shamim U, Uppilli B, Sharma P et al (2021) NephQuest Consortium. Next- generation sequencing for congenital nephrotic syndrome: a multi-center cross-sectional study from India. Indian Pediatr 58:445–451
Taniguchi Y, Nagano C, Sekiguchi K, Tashiro A, Sugawara N, Sakaguchi H et al (2021) Clear evidence of LAMA5 gene biallelic truncating variants causing infantile nephrotic syndrome. Kidney360 2:1968–1978
Braun DA, Warejko JK, Ashraf S, Tan W, Daga A, Schneider R et al (2019) Genetic variants in the LAMA5 gene in pediatric nephrotic syndrome. Nephrol Dial Transplant 34:485–493
Jones LK, Lam R, McKee KK, Aleksandrova M, Dowling J, Alexander SI et al (2020) A mutation affecting laminin alpha 5 polymerisation gives rise to a syndromic developmental disorder. Development 147:dev189183
Sunwoo Y, Choi N, Min J, Kim J, Ahn YH, Kang HG (2023) Case report: genetic defects in laminin α5 cause infantile steroid-resistant nephrotic syndrome. Front Pediatr 10:1054082
Author information
Authors and Affiliations
Contributions
BD, RRS, SK, and SK managed the patient, reviewed the literature, and drafted the manuscript. BD and RRS drafted the first version of the manuscript. DG interpreted the histopathological findings. KM interpreted the next generation sequencing results. All authors contributed to the review of literature, drafted the manuscript, and approved the final version of the manuscript. SK shall act as guarantor of the paper.
Corresponding author
Ethics declarations
Informed consent
Written informed consent for publication of the child’s clinical details was obtained from the patient’s parents.
Competing interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Deepthi, B., Sivakumar, R.R., Krishnasamy, S. et al. Congenital nephrotic syndrome with diffuse mesangial sclerosis caused by compound heterozygous mutation in LAMA5 gene. Pediatr Nephrol 39, 1421–1425 (2024). https://doi.org/10.1007/s00467-023-06223-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-023-06223-2