Disease relevance of LAMB2

• These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome [1].
• The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval [1].
• A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2 [2].
• OBJECTIVE: 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 [3].
• Because of its prognostic relevance, we advocate molecular genetic testing of LAMB2 in any case of prenatally detected nephrotic syndrome with negative results of NPHS1 mutational screening, especially in the presence of the typical sonomorphologic findings of the kidneys and the development of oligohydramnios [3].

High impact information on LAMB2

• S-laminin, a novel homolog of laminin, is concentrated in a subset of basal laminae including the basal lamina that passes between motor nerve terminals and muscle fibers at the neuromuscular junction [4].
• Laminin beta 2 (S-laminin): a new player at the synapse [5].
• S-laminin expression in adult and developing retinae: a potential cue for photoreceptor morphogenesis [6].
• Here, we narrow the ARMD1 locus to 14.9 Mb between LAMB2 and D1S3469, a region containing 50 known genes [7].
• In MN, the number of alpha4(IV) collagen, alpha1(IV) collagen, S-laminin or TGF-beta1 mRNA-expressing cells per glomerular cross-section was significantly larger than in controls (p< 0.05), and fibronectin mRNA was occasionally expressed in glomerular visceral epithelial cells (GECs) [8].

Chemical compound and disease context of LAMB2

• METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients) [9].

Biological context of LAMB2

• The human gene (LAMB2) was localized to chromosome 3p21 using somatic cell hybrids and fluorescent in situ hybridization analysis [10].
• Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children [1].
• CONCLUSION: This observation demonstrates that the phenotypic spectrum of LAMB2-associated disorders is broader than previously anticipated, and suggests that milder, non-lethal phenotypes may be associated with mutations retaining some residual function [2].
• In situ hybridization analysis of genes coding collagen IV alpha1 chain, laminin beta1 chain, and S-laminin in prostate tissue and prostate cancer: increased basement membrane gene expression in high-grade and metastatic lesions [11].

Anatomical context of LAMB2

• The human laminin beta 2 chain (S-laminin): structure, expression in fetal tissues and chromosomal assignment of the LAMB2 gene [10].
• The condition is caused by mutations in the LAMB2 gene leading to complete loss of function of the gene product laminin beta2, an essential component of the glomerular and other basement membranes [2].
• Although LAMB2 is known to be expressed in the neuromuscular system, and defects of the neuromuscular junctions had been found in laminin beta2-deficient mice, no consistent neurological phenotype has been described clinically in murine or human laminin beta2-deficiency before [12].
• Similar to vascular smooth muscle, the expression of A and S laminin chains in SMCs of the intestine was developmentally regulated [13].
• Biosynthesis and secretion of laminin and S-laminin by human prostate carcinoma cell lines [14].

Associations of LAMB2 with chemical compounds

• Restriction of axon growth to the developing NMJ and formation of active zones for ACh release in the presynaptic terminal may be induced by molecules in the synaptic basal lamina, such as S-laminin, heparin binding growth factors, and agrin [15].

Other interactions of LAMB2

• High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity [9].

Analytical, diagnostic and therapeutic context of LAMB2

• METHODS: In the present study, we used in situ hybridization techniques to determine steady-state levels of genes coding BM components (alpha1 chain of collagen IV, laminin beta1 chain, and S-laminin) in prostate tissue obtained from 15 radical prostatectomy specimens and 5 lymph node metastases of common prostatic adenocarcinomas [11].
• Comparing PAP smear cytology, aided visual inspection, screening colposcopy, cervicography and HPV testing as optional screening tools in Latin America. Study design and baseline data of the LAMS study [16].
• Measurement of PM10/2.5 fractionated respirable particles in urban Toronto by INAA, PIXE, ICP-AES, and LAMS. A comparison [17].

References