The phenotypic variance of patients with congenital nephrotic syndrome with nephrin and podocin mutations resulting from triallelic mutations represents an important advance in our understanding of the effect of multiple genetic mutations on clinical disease expression.
Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes the laminin beta2 chain, and is clinically characterized by congenital nephrotic syndrome (CNS) and bilateral microcoria.
Mutation of the LAMB2 gene is associated with Pierson syndrome, which is an autosomal recessive disorder characterized by congenital nephrotic syndrome and ocular abnormalities.
What is known • LAMB2 mutations are associated with Pierson syndrome • Pierson syndrome is associated with congenital nephrotic syndrome, microcoria and neurological deficits What is new • A novel mutation in the LAMB2 gene in two female siblings • Genotype and clinical phenotype description of a novel LAMB2 mutation.
In contrast, patients with LAMB2 missense mutations, such as R246Q, can have less severe extrarenal defects but still exhibit congenital nephrotic syndrome.
To describe the prenatal findings in Pierson syndrome, a newly defined autosomal recessive entity, comprising congenital nephrotic syndrome (CNS) with diffuse mesangial sclerosis and distinct eye abnormalities due to LAMB2 mutations.
The genetic evaluation revealed a heterozygous variant in NPHS1 (p.Arg207Trp), in NPHS2 (p.Ser95Phe) as well as in PLCE1 (p.Ala1045Ser) and did not explain CNS.
Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome.
Mutations in NPHS1, which encodes nephrin, are the main causes of congenital nephrotic syndrome (CNS) in Finnish patients, whereas mutations in NPHS2, which encodes podocin, are typically responsible for childhood-onset steroid-resistant nephrotic syndrome in European populations.
We describe a severe form of congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations caused by two truncating mutations in the gene encoding the laminin beta2 subunit (LAMB2).
Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities and neurodevelopmental delay (Pierson Syndrome).
Congenital nephrotic syndrome (CNS) is primarily a monogenetic disease, with the majority of cases due to changes in five different genes: the nephrin (NPHS1), podocin (NPHS2), Wilms tumor 1 (WT1), laminin ß2 (LAMB2), and phospholipase C epsilon 1 (PLCE1, NPHS3) gene.
Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities.
NPHS2 mutations were the most frequent cause of nephrotic syndrome among both families with congenital nephrotic syndrome (39.1%) and infantile nephrotic syndrome (35.3%), whereas NPHS1 mutations were solely found in patients with congenital onset.
These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.
The evidence that gene mutations in the polarity determinant Crumbs homologs-2 (CRB2) cause congenital nephrotic syndrome suggests the functional importance of this gene product in podocyte development.
Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessively inherited disease characterised by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin.
To date only six patients are reported: all carried homozygous ITGA3 mutations and presented a dramatically severe phenotype leading to death before age 2 years, from multi-organ failure due to interstitial lung disease and congenital nephrotic syndrome.