ABSTRACT
Objective:To report two cases of steroid-resistant nephrotic syndrome (SRNS) caused by LAMB2 gene mutation, and summarize the characteristics of genotype, clinical and pathological phenotypes of children with LAMB2 gene mutation. Methods:Two cases with SRNS caused by LAMB2 gene mutation were from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in December 2013 and September 2019. The demographic, family history and clinical data of two cases were collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. PubMed, Medline, CNKI and Wanfang databases were searched to summarize the clinicopathological phenotypes and genotypes of patients with LAMB2 mutation. Results:Among the two cases with SRNS caused by LAMB2 gene mutation, the clinical phenotypes were all manifested as nephrotic level of proteinuria and hypoalbuminemia, and there was no extrarenal clinical manifestation. One case presented with basement membrane delamination and the other with focal segmental glomerulosclerosis (FSGS). LAMB2 mutations of two cases were Exon32 c.5390G>T(p.Cys1797Phe), Exon19 c.2557C>T(p.Arg853*) and Exon27 c.4370G>A(p.R1457Q), Exon23 c.3325G>A(p.E1109K), respectively. In literature retrieval, there were 37 cases with LAMB2 gene mutation, including 24 cases with renal biopsy data, 13 cases of focal segmental glomerulosclerosis (FSGS), 4 cases of minimal change disease, one case of diffuse mesangial sclerosis, one case of IgM nephropathy, two cases of thin basement membrane nephropathy, and three cases of mesangial hyperplasia. Among them, eight cases had basement membrane delamination tear. Among the 37 cases, 11 cases were homozygous, 22 cases were complex heterozygosity, and 4 cases were heterozygous mutation. Conclusions:LAMB2 mutation may cause delamination tear of glomerular basement membrane. The clinical phenotype is congenital nephrotic syndrome or SRNS. The literature review shows the extrarenal manifestations caused by LAMB2 mutation are mostly various ocular abnormalities, as well as respiratory, digestive and nervous system abnormalities, and the time of progression to end-stage renal disease is also different.
ABSTRACT
En los últimos años se han identificado muchos síndromes nefróticos familiares y esporádicos que no responden a los tratamientos habituales (esteroides e inmunosupresores), evolucionan con relativa rapidez a la insuficiencia renal crónica y se producen por mutaciones genéticas. La mayoría de los síndromes nefróticos que se trasmiten genéticamente y que pueden ser congénitos, presentarse en el primer año de la vida, o en el niño mayor, son atribuidos a mutaciones en los genes NPHS1, NPHS2, WT1 y LAMB2. Otros síndromes nefróticos producidos por mutaciones genéticas pueden no manifestarse hasta la adultez. El objetivo fundamental de esta revisión fue llamar la atención sobre los síndromes nefróticos producidos por mutaciones genéticas en los que no sólo no se obtienen resultados con los tratamientos inmunosupresores, si no en los que dichos tratamientos pueden ser perjudiciales para el paciente
In past years many familial and sporadic nephrotic syndromes refractory to usual treatments (steroids and immunosuppressives), evolve quickly to a chronic renal failure produced by genetic mutations. Most of nephrotic syndromes genetically transmitted and that may be congenital, present in the first year of life or in the older child, are attributable to NPHS1, NPHS2, WT1 and KLAMB2 gen mutations. Other nephrotic syndromes produced by genetic mutations may not appear until adulthood. The main objective of present review was to alert on the nephrotic syndromes produced by genetic mutations without response to immunosuppressive treatments, but on those in which such treatment may be dangerous for patient