Résumé :
|
Arthrogryposis multiplex congenita (AMC) is caused by reduced fetal mouvements in utero. It describes congenital joint contractures present in more than one body area at birth. Neuromuscular types of AMC are basically linked to anterior horn cell and neuromuscular junction disease and sarcomeric anomalies. A genetic origin seems likely in the vast majority of neuromuscular AMC, but only a few genes have been currently identified. In addition, there is an overlap of congenital myopathy and AMC, and some mutations in ryanodine receptor 1 (RYR1) have been described as resulting in congenital myopathy with AMC. RYR1 is one of the major actors in transducing the electrical signal generated at the neuromuscular junction to the sarcomeric myofilaments. It is part of the calcium release complex (CRC) that is composed of other proteins involved in excitation contraction coupling : dihydropyridine receptor, triadin, calsequestrin, junctin. Hitherto genes involved in neuromuscular types of AMC have been documented to be expressed early or exclusively during embryonic or fetal development, thus explaining the very severe phenotype in some cases and the nonprogressive nature of joint contractures after birth in others. Yet, the expression pattern of CRC coding genes and proteins during muscle development is unknown. Therefore we are studying the fetal expression pattern of these genes and proteins in human skeletal muscle. Psoas and quadriceps samples were obtained from abortions or fetal deaths after informed consent was obtained from parents. Samples with a confirmed or suspected neuromuscular origin were discarded. Western blot analysis was performed with monoclonal or polyclonal antibodies directed against RYR1, DHPR-_1S, triadin, calsequestrin, and junctin. Transcripts of the coding genes were analysed by qPCR. The fetal expression pattern of the CRC proteins and their genes in human skeletal muscle should give new insights into the physiopathological mecanisms of congenital myopathies and arthrogryposis linked to RYR1 mutations and could yield new candidate genes for these two clinical entities.
|