[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

Analyse moleculaire de 10 familles atteintes de myopathie de Duchenne

We report the result of screening for molecular deletions in the dystrophin gene and of carriers determination in 120 individuals encompassing 16 boys with DMD in 10 families from SFAX and south of Tunisia. Deletions in DNA from boys with DMD were detected by PCR with series of 18 specific exon primers. We have determined carriers by PCR using CA repeat polymorphism and we have confirmed results obtained with first methods by southern blot analysis using Hind III and specific probes. results revealed variable deletions in 12-13 and 45 to 52 exons and 10 carriers

use of non-radioactive probes in the detection of human immunoglobulin genes

Contrarily to the radioactive probes, the nonradioactive ones are very stable and do not present any danger to health. This raised the need of the present work which aimed at preparing nonradioactive DNA probes which are then used to detect human immunoglobulin alpha genes. For this, DNA probes recognized by a specific antibody were prepared bearing the alkaline phosphatase [Digoxigenin-11-dUTP method] and then this probe was used for the detection of the cloned and genomic human immunoglobulin alpha genes. The results obtained, for the first time in this context, are in good correlation with the radioactive labeling tests. Thus, it is possible now to use nonradioactive technique to study the human immunoglobulin polymorphisms and the genetic diseases by restriction fragment length polymorphism [RFLP] without the known hazards of radioactivity

Rearrangement of immunoglobulins genes in the alpha heavy chain diseases: monoclonality criteria

We have studied the configuration of genes encoding for the heavy and light chains in the tumoral cells of 6 patients affected by alpha heavy chain disease [alpha HCD]. The results showed the presence of rearrangement of the alpha heavy chain as well as the kappa light chain genes whereas the lambda genes were in germinal configuration. Thus, these results suggest the presence of a monoclonal compound in the tumoral cells in the alpha HCD