This gene is part of a 500 kb inverted duplication on chromosome 5q. Spinal muscular atrophy diagnosis and carrier screening from. Ngs reads aligned to smn1 and smn2 exon 7 were quantified to determine. The smn1 gene provides instructions for making the survival motor neuron smn protein. This protein is one of a group of proteins called the smn complex, which is important for the maintenance of specialized nerve cells called motor neurons. Copy number variations in smn1 and smn2 are, respectively, associated with the. Smn1 survival of motor neuron 1, telomeric gene gtr ncbi. A new method for smn1 and hybrid smn gene analysis in spinal. Determination of smn1smn2 gene dosage by a quantitative. Genotypephenotype correlation in spinal muscular atrophy linked to smn1. School of medicine and global center of excellence coe program, tokyo. The sma identified program, sponsored by biogen and offered through invitae, provides no charge genetic testing to individuals suspected of having. Due to the near identical sequences of smn1 and smn2, analysis of this region.
The amplidex pcrce smn1 2 plus kit revolutionizes the analysis of these two genes by delivering comprehensive results in less than four hours. The copy numbers in exon 7 of smn1 gene matched with mlpa. Detection of homozygous deletion of exon 5 of naip gene. Inverse correlation between smn1 and smn2 copy numbers. Proportion of patients with the clinical picture of proximal sma displaying mutations of the smn1 gene. Smn1 gene copy number analysis for spinal muscular atrophy sma in a turkish cohort by codeseq technology, an integrated solution. Spinal muscular atrophy sma, caused by loss of the smn1 gene, is a. Pcrbased methods have been widely used in genetic testing for sma. We succeeded in developing the test so that gene specific primers amplify only smn1 but not smn2 or vice versa. Smn2, a copy gene, influences the severity of sma and may be used in somatic gene.
The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. Smn1 gene copy number analysis for spinal muscular atrophy sma. Spinal muscular atrophy sma is the second most common fatal autosomal recessive disorder with a carrier frequency of 1 in 5457 in all populations and incidence of 1 in 6,000 to 10,000 live births. Sma identified program spinal muscular atrophy genetic testing. It is a serious condition that gets worse as over time and is caused by mutations in both copies of the smn1 gene located on chromosome 5. Spinal muscular atrophy and the difficult smn1 gene.
Out of these, all parents and three of the four sibs had one smn1 gene copy and one sib had two smn1 gene copies table 1. Spinal muscular atrophy diagnosis and carrier screening. Introduction spinal muscular atrophy sma is a genetic disorder characterized by symmetric proximal muscle weakness due to degeneration of the anterior horn cells of the spinal cord. The smn protein is found throughout the body, with highest levels in the spinal cord. Smn1 is duplicated in a highly homologous gene called smn2 and both genes are transcribed lefebvre et al. The frequency of smn gene variants lacking exon 7 and 8 is highly. Louis viollet, judith melki, in handbook of clinical neurology, 20.
The next generation of populationbased spinal muscular atrophy. Smn1 gene copy number analysis for spinal muscular atrophy. Spinal muscular atrophy sma is one of the most prevalent genetic disorders in caucasians. A new method for smn1 and hybrid smn gene analysis in. Bmc medical genetics, may 2005 akanchha kesari, hanna rennert, debra gb leonard. Asuragen has launched the amplidex pcrce smn1 2 plus kit, which according to the company provides the most comprehensive analysis of genes associated with spinal muscular atrophy sma on the market and does so in a matter of hours. We first determined the absolute gene dosages sum of smn1. Smn1 dosage analysis in spinal muscular atrophy from india. Genetic pattern of smn1, smn2, and naip genes in prognosis.
Powered by amplidex technology, the assay accurately quantifies smn1 and smn2 exon 7 copy number and also detects smn1 gene duplication and smn2 disease modifier variants all from a single reaction. Read more about genetic testing available for diagnostics of spinal. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. Quantitative analyses of smn1 and smn2 based on realtime. Spinal muscular atrophy sma, caused by loss of the smn1 gene, is a leading cause of early childhood death. Fourteen samples in group i cases 16 were from the parents and sibs of sma patients with homozygous deletion of both exons 7 and 8 of smn1 gene. The sensitivity for smn1 deletion and sequence analysis for the detection of sma types iiii is probably almost 100% in a clinically welldefined patient group. The smn2 gene is present in all patients but is not able to compensate for the smn1 gene defects. Mutation surveyor software, quantitative analysis, sanger dna. Pcrrflp analysis showed homozygous deletion of exon 7 of smn1 gene in all the 44 patients. Sma, smn1 gene, gene conversion, molecular analysis. Smn1 is the only gene able to produce the fulllength smn protein that is.
Due to the near identical sequences of smn1 and smn2, analysis of this region is. The survival motor neuron gene 1 smn1 encodes the fulllength, and functional. Sip1 is not involved in the phenotypic variability of spinal muscular atrophy sma smn1 dosage analysis in spinal muscular atrophy from india. New sma screening kit quickly and thoroughly analyzes smn1. In group ii cases 710, carrier analysis was performed on the basis of family history of sma. Spinal muscular atrophy sma is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 smn1. Pcrce smn12 plus kit revolutionizes the analysis of these two genes by.
Smn1 dosage analysis is frequently requested in the context of genetic counseling, either as carrier testing or as a means of identifying patients with compound mutations deletions and intragenic smn1 mutation. Cn of smn1 and smn2 using genome sequencing gs data by analyzing read. Smnnegative spinal muscular atrophy panel centopedia. Intragenic mutations and hybrid smn gene analysis by sequencing. Spinal muscular atrophy sma is an autosomal recessive neuromuscular disorder characterized by motor neuron degeneration leading to muscular. Sequencing data were analyzed using sequencing analysis software v.
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