Locations of the LAMB2 mutations and molecular structure of laminin-521. a.
exon-intron organization of LAMB2 gene. The positions of two mutations found in the affected individual are indicated by arrows.
b. structure of laminin (LM)-521 and locations of mutations. Laminin is a large cruciform heterotrimeric glycoprotein and comprises basal membranes. LAMB2 encodes a Laminin subunit β2. It is a principal component of heterotrimer laminin α5β2γ1, which serves as a predominant extracellular matrix for mature GBM. The laminin α5β2γ1 is now referred to as LM-521 in the new nomenclature . Trimers are stabilized via the coiled-coil long arm, while short arms are composed of globular and intervening LE domains and vary in size among the distinctive subunits. LE: laminin-type epidermal growth factor-like modules; G:globular domain The patient has biallelic LAMB2 mutations: one truncates C-terminal 90 amino acids (red arrow), while another incorporates an earlier termination codon at N terminal one thirds position of β2 subunit through a splice error in a splice-donor +1 site of exon 9 (blue arrow). Both mutations likely induce a nonsense-mediated mRNA decay (NMD). The biallelic LAMB2 mutations together impaired the assembly of the LM-521, thereby accounting for developmental abnormalities