[Novel mutations in LAMA2 gene responsible for a severe phenotype of congenital muscular dystrophy in two tunisian families]

Congenital muscular dystrophies are a group of common genetically determined disorders often transmitted with a recessive mode of inheritance. In recent years, several deficiencies of proteins from the muscle membrane, extra cellular matrix, sarcomere, muscle cytosol and the nucleus have been described to cause CMD. The occidental type of CMD [MDC1A] in which the primary defect is a deficiency in laminin alpha 2 chain [merosin] encoded by LAMA2 gene, accounts for 30-40% of cases. The clinical course of CMD with complete laminin alpha 2 chain deficiency may be variable but most often; severe forms characterized by hypotonia at birth, profound muscle weakness, marked delay in motor milestones are observed. Since the identification of the first LAMA2 gene mutations leading to merosin deficiency in 1995, several mutations have subsequently been reported in many exons of this gene without any "hotspot" region. In this work, we report two novel homozygous mutations c.8005delT and C.8244+1G>A in the LAMA2 gene in four Tunisian patients with a severe MDC1A phenotype belonging to two unrelated consanguineous families

Hepatocellular carcinoma cell type specific interaction of P105 and P98 nuclear factors with laminin B1 and B2 genes.

Laminin is a major glycoprotein specific to basement membranes. Hepatocellular carcinoma tissue synthesize and secrete abundant laminin. By DNA-protein interaction assays, we have identified nuclear factors specific to hepatocellular carcinoma cells. The comparison of nuclear factor binding by Southwestern analysis with B1 and B2 laminin promoters revealed different patterns of nuclear factor binding in different cells types. In hepatocellular carcinoma, HepG2 cells, a specific pair of proteins (P105 and P98) consisting of 105 and 98 kDa were identified as common nuclear factors for both B1 and B2 laminin promoters, while in completely diverse human glioma cells (U251), various different and greater number of nuclear proteins ranging from 212 to 68 kDa were detected to interact separately with laminin B1 and B2 genes.

Hormone-mediated positive and negative regulation of a silencer region containing laminin B2 promoter in astrocytes.

Primary astrocytes synthesize only B2 chain (200 Kda) of laminin, which is one of the major components of basement membranes in the central nervous system (CNS). In CNS, B2 laminin functions as a potent neurite growth factor. Laminin B2 promoter contain no TATA or CAAT boxes but is GC rich. By deletion analysis and transient transfection assays of B2 laminin promoter, we have identified a silencer-like activity in the upstream region of the promoter. Thyroid hormone, insulin and phorbol ester mediated the induction of the promoter activity. Induction was repressed by the treatment of astrocytes with synthetic glucocorticoid hormone, dexamethasone. Hormone-mediated regulation through specific positive and negative responsive elements in transactivation of this silencer-containing TATA-less laminin B2 gene has been postulated.