ABSTRACT
OBJECTIVE: Spinal muscular atrophy (SMA) is a common and fatal autosomal recessive disorder. Approximately 94% of SMA patients are caused by homozygous deletion of SMN1 gene. SMA carrier screening is recommended considering the high carrier frequency (1 in 35-50) as well as severity of the disease. METHODS: A prospective population-based cohort study was carried out on 4719 pregnant women from Shanghai region. Copy numbers of SMN1 and SMN2 genes were effectively determined with denaturing high performance liquid chromatography (DHPLC) technique. The method has detected 94% of SMA cases with deletion or conversion of the SMN1 genes. RESULTS: Ninety SMA carriers with only one copy of the SMN1 gene were identified among the 4719 pregnant woman. The carrier rate was 1.9%. Respectively, 1.2% and 0.6% of the carriers were caused by SMN1 gene deletion and SMN1 gene conversion. CONCLUSION: Through this study, we have determined the frequency of SMA mutation carriers in a population of pregnant women. The result may provide a basis for genetic counseling in order to reduce the rate of SMA affected births.
Subject(s)
Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/genetics , Adult , China , Female , Gene Deletion , Genetic Testing/methods , Humans , Pregnancy , Prenatal Diagnosis/methods , Prospective Studies , Survival of Motor Neuron 1 Protein/genetics , Survival of Motor Neuron 2 Protein/genetics , Young AdultABSTRACT
Previous studies have demonstrated that end-organ deprivation after peripheral nerve injury results in targeting of regenerating nerve fibers into inappropriate pathways, which leads to poor functional recovery. Here we studied the effect of electrical stimulation on the regeneration selectivity of motor nerves after peripheral nerve injury and end-organ deprivation. We found that end-organ deprivation reduced regenerating selectivity of motor nerves, total number of regenerating motoneurons, and level of neural trophic factors in the regenerating pathways after nerve injury (p < 0.05). Electrical stimulation successfully promoted motor nerve regeneration selectivity regardless of end-organ connections (p < 0.05). This increased selectivity was accompanied by an increase in the protein level of neural trophic factors in the distal nerve stumps by 3 weeks after nerve injury (p < 0.05). There was a similar increase in the protein level of these neural trophic factors in denervated muscle. However, the RNA level of these factors decreased both in the distal nerves and in the muscle. Despite the promising effect of promoting motor nerve regeneration selectivity, electrical stimulation did not prevent motoneuron loss caused by end-organ deprivation. The present study suggests that end organs contribute to the development of selective motor nerve regeneration by increasing the neurotrophic factors in the regeneration pathways. Electrical stimulation is an efficient strategy to ameliorate the deteriorated regeneration microenvironment caused by end-organ deprivation and to promote motor nerve regeneration selectivity when end-organ connections are deprived.