ABSTRACT
Spinal muscular atrophy (SMA) is a severe neuromuscular disease. It is a common cause of infant mortality. Its incidence is estimated at 1 in 10,000. Clinically, age of onset and the symptoms can distinguish four types of SMA. The objective of this study is to make available to clinicians a reliable and reproducible test for the molecular diagnosis of SMA. We evaluate the benefits and limitations of three tests used in our laboratory (RFLP-PCR, sequencing, and qPCR).
Subject(s)
Genetic Testing/methods , Muscular Atrophy, Spinal/diagnosis , Polymorphism, Restriction Fragment Length , Sequence Analysis, DNA , Child , Child, Preschool , Female , Humans , Infant , Male , Molecular Diagnostic Techniques/methods , Muscular Atrophy, Spinal/genetics , Polymerase Chain Reaction , Sensitivity and Specificity , Survival of Motor Neuron 1 Protein/genetics , Survival of Motor Neuron 2 Protein/geneticsSubject(s)
Carrier Proteins/genetics , DNA Mutational Analysis/methods , Genetic Counseling , Spinocerebellar Ataxias/genetics , Vitamin E Deficiency/genetics , Chromosomes, Human, Pair 8/genetics , Consanguinity , Deoxyribonucleases, Type II Site-Specific , Female , Genetic Testing , Humans , Intestinal Absorption/genetics , Male , Morocco/epidemiology , Polymorphism, Restriction Fragment Length , Prevalence , Sequence Deletion , Spinocerebellar Ataxias/drug therapy , Spinocerebellar Ataxias/epidemiology , Spinocerebellar Ataxias/prevention & control , Vitamin E/pharmacokinetics , Vitamin E/therapeutic use , Vitamin E Deficiency/drug therapy , Vitamin E Deficiency/epidemiology , Vitamin E Deficiency/prevention & controlABSTRACT
Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a highly variable clinical course and prognosis. We report on the cases of three siblings with SMA. The weakness muscular observes at three siblings but more earlier and severe to the index case with a fast evolution towards respiratory distress syndrome resulting in its death at 5 years. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene were found in all three siblings. No child showed deletion of NAIP gene. Muscular weakness and respiratory distress severity however were different among the siblings. The index patient died at the age of 5 because of respiratory insufficiency. Several molecular mechanisms may be involved in such phenotypic variability. The PCR-RFLP method allows to confirm clinical diagnosis of SMA in children, while avoiding more invasive methods such as EMG and muscular biopsy. However, this diagnostic tool does not allow yet the distinction between different clinical forms of SMA.
Subject(s)
Cyclic AMP Response Element-Binding Protein , Muscular Atrophy, Spinal/genetics , Nerve Tissue Proteins , Neuronal Apoptosis-Inhibitory Protein , RNA-Binding Proteins , Child , Child, Preschool , Female , Gene Amplification , Gene Deletion , Genotype , Humans , Male , Morocco , Muscular Atrophy, Spinal/diagnosis , Mutation , Pedigree , Phenotype , Polymerase Chain Reaction , SMN Complex ProteinsABSTRACT
The common prion protein gene (PRNP) codon 129 polymorphism is a strong susceptibility factor for human prion diseases. In this study, we examined the allelic variation of methionine and valine at codon 129 in 147 subjects representing the normal Moroccan population. The sharing of the genotype was 57.1% for Methionine-Methionine (MM), 36% for Methionine-Valine (MV), and 6, 8% for Valine-Valine (VV). These results are indeed intermediate between those discovered at the European and Asian populations. However, and for a better assessment of the risk to develop prion diseases in the Moroccan population, the survey of the frequency of the codon 219 polymorphism is required.
