The gene LAMB2 encodes laminin beta2 which belongs to a group of cross-shaped heterotrimeric proteins called laminins, each consisting of alpha, beta, and gamma subunits joined together through a coiled coil. Laminins are very important basement membrane components with roles in cell adhesion, proliferation, differentiation and migration. The protein LAMB2 has 1,798 amino acids, with an N-terminal globular laminin domain for interacting with neighboring laminins, multiple EGF-like repeats with an interjacent second globular domain, and a coiled coil domain. The 32 amino acids at the N-terminus form a cleavable signal peptide. LAMB2 is expressed in the glomerular basement membrane, ocular structures and the neuromuscular junctions.
The LAMB2 gene maps to 3p21 and is composed of 32 exons spanning about 12 kb of genomic DNA. Mutations affecting the gene LAMB2 lead to lack of laminin beta2, which in turn causes Pierson syndrome. Partial reduction in laminin beta2 can cause a milder form of the abovementioned syndrome, which involves congenital nephrotic syndrome with a complex ocular maldevelopment, the most striking feature of which is extreme narrowing of the pupils (microcoria). The majority of LAMB2 mutations are predicted to lead to a premature translational stop codon.
Mbarek et al. (2011) analyzed 24 children belonging to 13 families with steroid-resistant nephrotic syndrome (SRNS) manifesting with various ages of onset. They found two novel pathogenic mutations in the LAMB2 gene in two families; p.E705X and p.D1151fsX23. At the time, these aberrations represent the first cases of LAMB2 mutations in Tunisia. Nine of 24 patients failed to be categorized by mutational analysis.