A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome

Abstract

BackgroundPierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin β2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype–phenotype correlations have been reported, often with great clinical variability. We hereby report a novel homozygous nonsense mutation in the LAMB2 gene, associated with a severe phenotype presentation.Case diagnosisWe describe a term male infant born from consanguineous parents. The mother previously lost three children in the neonatal period, secondary to undefined renal disease, had two spontaneous abortions, and gave birth to one healthy daughter. The index case presented at birth with bilateral microcoria, severe hypotonia, respiratory distress, and congenital nephrotic syndrome associated with anuria and severe renal failure requiring peritoneal dialysis. The patients’ clinical follow-up was unfavorable, and the newborn died at 7 days of life, after withdrawal of life support. Genetic analysis revealed a homozygous nonsense mutation at position c.2890C>T causing a premature stop codon (p.R964*) in LAMB2 gene.ConclusionWe here describe a novel nonsense homozygous mutation in LAMB2 gene causing a severe neonatal presentation of Pierson syndrome. This new mutation expands the genotype–phenotype spectrum of this rare disease and confirms that truncating mutations might be associated with severe clinical features.

Recent advances of animal model of focal segmental glomerulosclerosis

“…Myosin 1e (Myo1e) is one of the two Src homology 3 domain-containing "long-tailed" type I myosins in Actin filament cross-linking protein/Interacts with integrins and strengthens the podocyte-GBM interaction Atypical protein kinase C [68][69][70][71] Tight junctions/Formation of Par complex and interacts with slit diaphragm Rhophilin-1 [80] Rho GTPase activating protein 24 [80] Cytoplasm/Rho GTPase-interacting protein, integrity of glomerular filtration barrier Angiotensin II receptor [55][56][57] Angiotensin-converting enzyme [55][56][57] Membrane/pseudocyst formation at podocyte CD2-associated protein [65][66][67] CD2-associated protein [64] Insertion site of the slit diaphragm/Formation SD complex with podocin and nephrin Laminin subunit beta-2 [81][82][83][84] Laminin subunit beta-2 [81][82][83][84] Podocyte anchoring and differentiation in GBM microRNA 193α [74,75] Cytoplasm/Inhibition of expression of WT-1 Myosin 1e [49,50] Myosin 1e [49,50] Actin binding long-tailed motor protein/Regulation of actin cytoskeleton Nuclear factor of activated T cells [76,77] Transient receptor potential 6 [53,54] Membrane/the activation of calcineurin-NFAT/Wnt signaling via the increased calcium influx Podocin [46] Podocin [58,59] Insertion site of the SD/SD assembly and maintaining the signaling of nephrin Shroom family member 3 …”

“…Most affected children exhibit early onset of chronic renal failure, neurodevelopmental deficits, and blindness. It is caused by a homozygous or compound heterozygous mutation in the gene encoding laminin beta2 (LAMB2) on chromosome 3p21 [82,83]. This mutation was proved in animal model which showed mesangial sclerosis and highly expressed LMB2 in basement membrane [84] ( Table 2; Fig.…”

Kidney transplantation in a child with Pierson syndrome

“…However, the predominant onset age is within 3 months . Diffuse mesangial sclerosis and diffuse effacement of the foot processes constitute the most common microscopic findings in patients who underwent renal biopsy …”

“…Mutation of the LAMB2 gene—which is the rarest among all—is associated with Pierson syndrome . Less than 60 Pierson syndrome cases have been described in the literature so far . It is an autosomal recessive disorder first described by Pierson et al in 1963 .…”

“…It is an autosomal recessive disorder first described by Pierson et al in 1963 . It typically presents as CNS accompanied by ocular involvement …”