Advanced searches left 3/3
Search only database of 8 mil and more summaries

Smn1 Smn2

Summarized by PlexPage
Last Updated: 02 July 2021

* If you want to update the article please login/register

General | Latest Info

Spinal Muscular Atrophy is caused by a mutation in survival motor neuron 1 gene. This gene is responsible for producing survival motor neuron protein, which maintains health and normal function of motor neurons. In individuals with Spinal Muscular Atrophy, both copies of SMN1 gene are mutate, leading to decreased production of SMN protein. Without a proper level of SMN protein, motor neurons in the spinal cord will be lose, preventing muscles from receiving proper signals from the brain. Spinal Muscular Atrophy affects everyone differently, and it is important to note that symptoms can vary greatly according to age of onset and disease severity. Individuals may experience progressive muscle weakness in muscles closest to the center of the body, such as shoulders, thighs, and pelvis. These muscles enable activities such as head control / movement, sitting up, crawling, and walking. Breathing and swallowing may also be affect. It is believed that Spinal Muscular Atrophy does not affect neurons responsible for cognition, which is a mental process through which we gain knowledge and understanding through thought, experience, and senses. According to one study, children and adolescents with Spinal Muscular Atrophy have normal intelligence, with IQs in the standard range. For school - age children, special accommodation may be needed to help maintain cognitive and intellectual engagement. It is believed that Spinal Muscular Atrophy does not affect neurons responsible for cognition, which is a mental process through which we gain knowledge and understanding through thought, experience, and senses. According to one study, children and adolescents with Spinal Muscular Atrophy have normal intelligence, with IQs in the standard range. For school - age children, special accommodation may be needed to help maintain cognitive and intellectual engagement. All individuals with Spinal Muscular Atrophy have at least one backup gene, known as SMN2. The SMN2 gene has a similar structure to SMN1, but only a small amount of SMN protein it produces is fully functional. This low level of SMN protein is not effective enough to sustain survival of motor neurons in CNS. The number of SMN2 genes may vary, and higher SMN2 copy number is associated with less - severe symptoms of Spinal Muscular Atrophy. Nevertheless, disease has a wide range of symptoms and it is difficult to predict severity based on the number of SMN2 copies alone. Thus, experts recommend that care decisions be made based on individuals ' functional ability and not on SMN2 copy number alone. Discovery of this backup gene provides a unique opportunity for development of potential therapies that may help SMN2 gene produce more SMN protein. The number of SMN2 genes may vary, and higher SMN2 copy number is associated with less - severe symptoms of Spinal Muscular Atrophy. Nevertheless, disease has a wide range of symptoms and it is difficult to predict severity based on the number of SMN2 copies alone. Thus, experts recommend that care decisions be made based on individuals ' functional ability and not on SMN2 copy number alone.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Spinal muscular atrophy

Autosomal recessive disorder proximal spinal muscular atrophy is a severe neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, which results in progressive proximal muscle weakness and paralysis. Sma is the second most common fatal autosomal recessive disorder after cystic fibrosis, with esti. Mat prevalence of 1 in 10 000 live births and Carrier frequency of 1 / 401 / 60. Childhood SMA is subdivided into three clinical groups on basis of age of onset and clinical course: Type I SMA is characterized by severe, generalized muscle weakness and hypotonia AT birth or within first 3 months. Death from respiratory failure is usually oc. Curs within the first 2 years. Children with Type II are able to sit, although they cannot stand or walk unaided and survive beyond 4 years. Type III SMA is a milder form, with onset during infancy or youth: patients learn to walk unaided. The Survival Motor Neuron Gene comprises nine exons and has been shown to be the primary SMA determining Gene. Two almost identical SMN genes are present on 5q13: telomeric or SMN1 Gene, which is an SMA - determining Gene, and centromeric or SMN2 Gene. Smn1 Gene exon 7 is homozygously absent in approximately 95% of affected patients, with few exceptions,. Remainder are heterozygous for exon 7 deletion and small more subtle mutation in other allele.S Although abnormalities of SMN1 Gene are observed in the majority of patients, no phenotypegenotype correlation was observed because SMN1 exon 7 is absent in the majority of patients independent of type of SMA. This is because routine diagnostic methods do not distinguish between deletion of SMN1 and conversion event whereby SMN1 is replaced by a copy of SMN2. There have now been several studies that have shown that SMN2 copy number influences severity of disease. Copy number varies from zero to three copies in normal population, with approximately 15% of normal individuals having no SMN2. However, milder patients with Type II or III have been shown to have more copies of SMN2 than do Type I patients. It has been proposed that extra SMN2 in more mildly affected patients arise through gene conversions, whereby SMN2 gene is copied either partially or totally into telomeric locus. Five base pair changes exist between SMN1 and SMN2 transcripts, and none of these differences change amino acids. Because virtually all SMA individuals have AT least one SMN2 Gene copy, it was initially not understood why individuals with SMN1 mutations have an SMA phenotype. It has now been shown that the SMN1 Gene produces predominately full - length transcript, whereas the SMN2 copy produces predominately alternatively transcribed product. Inclusion of exon 7 in SMN1 transcripts and exclusion of this exon in SMN2 transcripts is caused by single nucleotide difference AT + 6in SMN exon 7.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

SMN1, SMN2

Progressive muscular atrophy is adult - onset Motor Neuron disease characterized by loss of LMNs. It is a rare and sporadic disorder that is clinically distinct from ALS even though subclinical involvement of UMNs has been observed in many PMA patients. Those PMA patients exhibiting more severe Clinical presentation tend to harbor higher SMN1 Copy numbers. No relationship between SMN2 Copy Number and disease severity was noted in these PMA patients. Moulard et al. Note that the frequency of SMN2 deletion was higher in a small group of patients with sporadic LMN disease.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Assay and technical information

We established a new array dPCR SMN1 and SMN2 Copy Number Assay that accurately measures copy numbers in SMA as well as in non - SMA DNA samples isolated from whole blood cells and cell lines derived from fibroblasts and lymphoblasts. Dpcr - derive SMN1 and SMN2 Copy numbers match those found in Reference standards used by diagnostic Laboratory and in a limited number of cases using microdroplet dPCR. Smn2 Copy numbers in SMA DNA samples were concordant with those results measured by TaqMan qPCR at low SMN2 Copy numbers but concordance was not as strong at higher SMN2 Copy numbers. The majority of dPCR / TaqMan qPCR mismatches occur at higher SMN2 Copy numbers where TaqMan qPCR Assay cannot easily distinguish unit differences. Array dPCR detects unit differences in SMN2 Copy numbers over a wide range of SMN2 Copy numbers similar to droplet dPCR. Because of this wide range of detection, dPCR can be very useful in accurately quantifying SMN2 Copy Number in patients with milder forms of SMA, that is, type III SMA, who generally have higher SMN2 Copy numbers. Reliability of array dPCR assays was determined by comparing coefficients of variation for all samples with the same copy number. Our array dPCR results had 1. 6 - 3. 7% CV for SMN1 and 2. 1 - 3. 7% CV for SMN2. In contrast, TaqMan qPCR Assay show 5. 2 - 9. 7% CV for SMN1 and 0. 8 - 7. 6% CV for SMN2. Greater reliability of array dPCR Assay when compared against TaqMan qPCR assays is the result of random distribution of template DNA molecules within 20 000 partitions in microfluidic dPCR array. Using array dPCR, we have confirmed a very strong inverse correlation between SMN2 Copy Number and disease severity in our SMA patient samples. Numerous previous studies also document a similar relationship between SMN2 Copy Number and SMA disease severity. Smn2 Copy Number is associated with many measures of SMA phenotype severity including gross motor function, force vital capacity, muscle mass, and denervation. Many current and future clinical trials for SMA will use these outcomes measures along with changes in SMN expression to gauge efficacy. Because SMN2 Copy Number is the defining criteria of eligibility for many SMA Clinical trials, accurate and reliable measurements will continue to be essential to Clinical Research. In some cases, within our pool of SMA samples, there were SMA patients with low SMN2 Copy numbers exhibiting milder phenotype. A rare variant in SMN2, SMN2 C. 859g > C, may explain this finding as it results in partial rescue of truncated, exon 7 exclude, transcript that characterizes most of the mRNA generated from SMN2. Array dPCR will aid in identification of cases having mismatches from expected genotype - phenotype relationship. Identifying such mismatches could lead to identification of potential complementing mutations in SMN2 like SMN2 C. 859g > C. Array dPCR can be easily used to measure SMN1 and SMN2 Copy numbers accurately in DNA samples obtained from SMA patients and healthy, non - SMA controls.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Results

Distributions of SMN genotypes in unaffected individuals are shown in Table 1. Smn2 copy number and SMN1 copy number correlate inversely in the general population. Smn2 copy number decreased to one or zero copies in 11 of 13 individuals with three or four copies of SMN1, whereas only 71 of 164 individuals with 2 SMN1 copies had one or zero SMN2 copies. There was notable tendency for SMA type I carriers to have fewer SMN2 copies, compared to type II and type III carriers. While only three of 177 noncarriers with two or more SMN1 copies had three SMN2 copies, SMN2 copy number was increased to three or four copies in 19 of 109 carriers with SMN1 deletion / conversion mutations. Distribution of SMN genotype in 32 SMA patients is as followed with genotype express as: among 16 type patients, three were 0: 1 and 13 were 0: 2; single type I - II patient was 0: 2; among eight type II patients, one was 0: 2 and seven were 0: 3 and one was 0. 4; and one patient with very mild adult - onset SMA was 0: 4. Smn2 copy numbers correlate inversely with disease severity.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Background

Spinal Muscular Atrophy is one of the most common autosomal recessive diseases and is characterized by degeneration of Spinal cord motor neurons, atrophy of skeletal muscles, and generalized weakness. The incidence of SMA is approximately 1 / 6 000 to 1 / 10 000 live births, and carrier frequency is about 1 / 42 in the Chinese population. Sma is divided into four clinical types according to age of onset and achieve motor function: severe type I; intermediate type II; mild type III; and adult - onset type IV. Sma is caused by dysfunction of survival Motor Neuron gene on chromosome 5q13. 2 Two versions of SMN, SMN1 and SMN2, differ by only five nucleotides. Smn1 produces full - length transcript that encodes functional SMN protein. About 94% of SMA patients have homozygous deletion of SMN1 exon 7. Smn1 can be absent because of deletion or SMN1 - To - SMN2 conversion. Single nucleotide transition in SMN2 exon 7 relative to SMN1 causes most of SMN2 pre - mRNA to lack exon 7 and encode nonfunctional SMN7 protein. However, about 10% of SMN2 pre - mRNA is normal and can be translated into full - length SMN protein. Smn2 partially functionally compensates for SMN1 homozygous deletion. Thus, SMN2 Copy number influences SMA severity. In addition to SMN genes, neuronal apoptosis inhibitory protein gene, also located At chromosome 5q13. 2, is SMA disease - related gene. Copy number of NAIP is reported to correlate with SMA severity. Sma patients with fewer copies of NAIP have more severe phenotypes than patients with more copies of NAIP. Moreover, both SMN2 and NAIP Copy numbers were associated with onset age, risk of death and survival probability of SMA patients. Therefore, elucidating gene copy numbers and structures of SMN1, SMN2 and NAIP is important for analyzing molecular mechanism of SMA and for SMA clinical diagnosis. Smn1, SMN2 and NAIP genes are all located at 5q13. 2, unstable chromosomal region that is prone to deletion, duplication, and gene conversion. Copy numbers of SMN1 and SMN2 vary in humans. In Chinese populations, up to 4 SMN1 or SMN2 genes are reported in both healthy people and SMA patients. In addition, SMN gene deletions and rearrangements are found in different populations. Detecting copies and gene structures of SMA - related genes is difficult because of the high homology between SMN1 and SMN2. However, multiple ligation - dependent probe amplification assay has been established for detecting deletions and duplications of SMA - related genes. To determine copy numbers and structures of SMA - related genes in the Chinese population, we analyzed SMN1, SMN2 and NAIP in 42 Chinese SMA patients and 212 Chinese healthy individuals using MLPA assays.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Methods

We call number of chromosomes carrying SMN1 and SMN2 bases by combining total SMN CN with read counts supporting each of gene - specific bases. At each SMN1 / 2 differentiating base, based on call copy number of intact SMN, caller iterates through all possible combinations of SMN1 and SMN2 copy numbers and derives a combination that produces the highest posterior probability for observed number of SMN1 and SMN2 supporting reads. Smn1 CNs calls on a single basis are then combined to make aggregate SMN1 CN calls based on consensus rule. In addition to calling CN of bases that are specific to either SMN1 or SMN2, this method can be applied to variant positions to identify copy number of bases known to be specific to one of two genes, eg, c. * 3 + 80T > G as described in the results.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Causes/Inheritance

Chromosome 5 - related SMA follows an inheritance pattern know as autosomal recessive. Diseases that are recessive require two gene flaws, usually one from each parent, but occasionally one from one parent and one that occurs as the fetus is being form. People who have only one gene flaw for recessive disease are said to be carriers and usually show no symptoms. Often, family has no idea that some members are carriers until a child is born with recessive disorder. If both parents are carriers of chromosome 5 gene flaw, risk of each pregnancy producing a child with disease is 25%. This risk doesnt change no matter how many children a couple has. Genetic testing for chromosome 5 - relate SMA is available for those suspected of having disease, including unborn babies, and for carriers of disease. Genetic testing is expanding and changing rapidly, but its implications can be complex. Its best to talk with genetic counselor before embarking on testing. It is imperative to diagnose SMA as early as possible, ideally before symptom onset, because delay in treatment can worsen the course of disease and create permanent damage to motor neurons. The best way to identify SMA before symptoms appear is to screen all newborns for SMN1 exon 7 deletion. Since Spinraza, disease - modifying therapy, was approved in 2016 by the US Food and Drug Administration and early treatment show positive outcomes, secretary of the US Department of Health approved the addition of SMA to Newborn Screening panels. 1 For more information, visit HYPERLINK https: / Mda. Org / SMA - add - National - List - Disorders - to - Screen - for. Sma added to the National List of Disorders to Screen for at Birth. X - link SMA is inherited via the X chromosome. Females have two X chromosomes, and those with gene flaw on one X chromosome are usually considered carriers of X - link Disease. Males, however, have no second X to protect them from full effects of gene flaw on the X chromosome and show full effects of such a flaw. Additionally, SMA can be caused by mutations in DYNC1H1 gene on chromosome 14. This form is dominantly inherit, meaning that only one DYNC1H1 gene mutation, inherited from one parent, is sufficient to cause disease. To read more about Genetics of SMA and Genetic testing for this Disease, also see: MDA Genetic Counseling Webinar Answers Key Questions, Quest News Online, Feb. 28 2012 Facts About Genetics and Neuromuscular Diseases, MDA, December 2009 Genie's Out of Bottle: Genetic testing in the 21st century, Quest Magazine, November 2008 Pain and Promise of Prenatal and Newborn Genetic Diagnosis, Quest Magazine, july 2007 baker, M. Et al. Maximizing Benefit of Life - Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening: Essential Steps. Jama Neurol. Doi: 10. 1001 / jamaneurol.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Introduction

We measure the number of SMN1 and SMN2 copies in gDNAs isolated from cell lines derived from SMA patients as well as from healthy non - SMA subjects using array dPCR. Smn1 or SMN2 dPCR was multiplexed with RPPH1 because copy number of RPPH1 does not vary amongst human population. Gdna templates were digested with Eco RI prior to PCR amplification as there are no Eco RI restriction sites within SMN1, SMN2 or RPPH1 regions of amplification. The Array dPCR assay detects accurately and reproducibly from 0 to 3 copies of SMN1 and 0 to 5 copies of SMN2 in analyzed samples. Assay conditions were first tested on SMN1 and SMN2 reference standards obtained from Clinical Laboratory Improvement Amendments - certified Molecular Diagnostics Laboratory at N / AIDHC. These standards were generated from genomic DNA extracted from blood specimens, with copy numbers assessed by QCEFA. One of these reference samples could not be accurately accessed For SMN2 copy number using QCEFA. Blind array dPCR determination of SMN1 and SMN2 copy numbers in reference samples match that obtained by QCEFA. Of interest, sample SDC1 measurements fell well within the detection capability of array dPCR and this sample carry 4 copies of SMN2. This validation phase also includes comparison between array dPCR and real - time TaqMan qPCR. Smn2 copy numbers for subset of our SMA samples were determined previously. We saw good concordance between the 2 techniques for samples carrying low SMN2 copy number; However, concordance dropped to 80% for samples carrying higher SMN2 copy numbers. This result highlights the inability of TaqMan qPCR to accurately measure copy numbers greated than 3. To test the upper limit of detection for this new assay, we used gDNA from a set of 4 SMA and 1 carrier coriell Cell Repositories Cell lines that were shown to contain 2 3 3 2, and 5 SMN2 copies, respectively, using droplet dPCR. Our copy number measurements were in complete concordance with published droplet dPCR results, most notably for GM03814 which carries high copy number of SMN2. To determine the reliability of array dPCR copy number assays, mean CV was calculated for each SMN1 and SMN2 copy number measurement for both SMA and non - SMA samples derived from cell lines. In both SMA and non - SMA samples, CVs for each SMN1 and SMN2 copy numbers were below 4%, demonstrating that our array dPCR copy number assays were reliable. Using these assay conditions, we determine copy numbers of SMN1 and SMN2 for all of the cell lines within our collection. Our collection contains both fibroblasts and Epstein - Barr virus immortalize LCLs. One hundred Cell lines63, of which were derived from SMA patients, were used in this study. All but one of 63 SMA DNA samples had loss of both SMN1 alleles as determined by using Sanger sequencing. Remaining cell lines harbor one deletion allele and one missense mutation in SMN1.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Discussion

Loss of both copies of exon 7 of survival of motor neuron Gene is the most common causative mutation of SMA. However, phenotype and clinical severity differ greatly. Modifier genes mapped to 5q13 chromosomal region were affirmed to play a crucial role in determination of disease severity. Being major modifier Gene of spinal muscular atrophy disease, higher SMN2 copy number, larger amount of full - length SMN Protein produce, and milder associated SMA phenotype. Also, NAIP Gene is another disease - modifying Gene, correlating with disease severity and duration of survival. In this study, we determined copy number variations of SMN2 and NAIP genes in 44 SMA Egyptian patients with homozygous deletion of exon 7 of SMN1 Gene. Genotype - phenotype correlation reveals that CNVs of exon 7 of SMN2 significantly decrease with an increase in disease severity. Copy number variations of exon 7 of SMN2 were 1 or 2 in type I SMA, whereas in type II SMA, CNVs of exon 7 of SMN2 Gene were 2 3, or > 3. Finally, 3 copies or more than 3 copies were detected in SMA III patients. Reveal data could not discriminate clearly between clinical types, specifically in patients with 3 or more than 3 copies. Although SMN2 is considered as a positive modifier, it could not be a clear - cut phenotype predictor. This finding was also concluded by Cypriotic study where phenotype could not be predicted by SMN2 copy number in Cypriot SMA patients. On the other hand, increasing number of patients might give better discrimination due to an increase in statistical values. Calucho and Bernal assume that prediction based on SMN2 CNVs could be better attempt on large Spanish cohort. Our results show that NAIP deletion alone also was not a good predictor of SMA severity as homozygous deletion was detected in 60% of type I SMA and in 73% of type III SMA, which was much lower than published ratios in other populations. In Tunisian, Iranian, Kuwaiti, Malaysian, and Cypriot patients, frequency of deletion of both SMN1 and NAIP genes in type I SMA patients range from 80 to 100% of patients. However, type I SMA patients with homozygous deletion of exon 5 of NAIP Gene have shown lower ratios of between 26% and 46% of German, Vietnamese, Chinese, and Serbian patients. It was noted that populations with higher parental consanguinity rates show higher frequency of NAIP Gene deletion. Therefore, deletion of NAIP Gene might be related more to the mechanism of SMN1 Gene deletion rather than phenotype. The combination of CNVs of exon 7 of SMN2 and deletion of exon 5 of NAIP genes reveal that they are closely related to the occurrence and development of spinal muscular atrophy in patients.


INTRODUCTION

Spinal muscular atrophy, autosomal recessive disorder characterized by loss of motor neurons in the anterior horn of the spinal cord, affects 1 in 10 000 live births. 1 All three types of SMA are caused by mutations in SMN1 on chromosome 5q13. 2 coding regions of SMN1 and its homologue, SMN2 differ on only one basis. 3 Although translationally silent, this transition 840C > T in SMN2 exon 7 alters the splicing pattern of SMN2 transcripts, resulting in a lower level of full - length SMN mRNA from SMN2 than from SMN1. 4 5 Recent evidence suggests that 840C > T in SMN2 activates exonic splicing silencer, which functions as a binding site for know repressor protein hnRNP A1. 6 Approximately 94% of clinically typical SMA patients lack both copies of SMN1 by either gene deletion or SMN1 - to - SMN2 gene conversion. 7 Approximately 30 small intragenic mutations have also been identify. 8 by SMN gene dosage analyse to identify SMA carriers with only one copy of SMN1, three copies of SMN1 have been identified in normal individuals, implying presence of two copies of SMN1 on single chromosome 5. 9 10 presence of this 2 - copy - SMN1 allele is associated with decreased SMN2 copy number. 11 Importantly, SMA carriers may have two copies of SMN1 on one chromosome 5 and deletion / conversion mutation of SMN1 on other chromosome 5. 10 by dosage analysis alone, such carriers, as well as carriers of small, intragenic mutations, are indistinguishable from normal individuals with one copy of SMN1 on each chromosome 5, unless monosomal analysis technique 12 is used. Adding to the complexity of SMA genetics is high de novo SMN1 mutation rate. 13 pericentromeric location 14 and presence of paralogous segmental duplication 15 likely predispose region to recombination events, leading to high observe de novo deletion mutation rate. Because of the genetic complexity of SMA and high carrier frequency, genetic counseling and risk assessment are essential components of genetic testing for SMA patients and their families. 16 However, previous risk - assessment studies were based on data derived from a relatively limited number of studies and subjects. 1 16 17 For the most accurate possible risk calculations, we meta - analyze all available and reliable data including our own new data to determine SMN1 allele frequencies and de novo SMN1 mutation rates. To better understand molecular evolution of the SMN region, we also estimate various SMN1 - SMN2 haplotype frequencies by haplotype reconstruction and meta - analysis.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Conclusions

We implement PCR - RFLP, multiplex PCR, and real - time PCR to analyze the correlation between CNVs of SMN1, NAIP, and SMN2 genes and SMA phenotype in Egyptian patients. Although we use three different molecular techniques to generate genotype of SMA patients, studies show preference for combination of modifier genes as prognostic genetic pattern for phenotype determination rather than using SMN2 CNVs only. Genetic patterns including SMN1, SMN2, and NAIP genes can help more in prognosis of more severe SMA types rather than less severe types. Moreover, determination of CNVs of exon 7 of SMN2 is of great importance in placement of effectiveness of new therapy, as it depends on having at least one copy of exon 7 of SMN2 gene.


4 Discussion

Identification of genotype constitution in patients diagnosed with SMA has important implications for genetic counseling of families with or without a history of disease. Approximately 94 - 95% of individuals with SMA are homozygous carriers of SMN1 exon 7 deletion. On the other hand, SMN2 is an SMA modifier gene, and a strong inverse correlation between its copy number and disease severity has been demonstrate: with larger number of copies, better prognosis and later age of onset. In our study, number of SMN2 copies and carrier frequency of SMN1 deletion in a random sample of Venezuelan populations were assess, as well as in families with presumptive diagnosis of SMA.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

logo

Plex.page is an Online Knowledge, where all the summaries are written by a machine. We aim to collect all the knowledge the World Wide Web has to offer.

Partners:
Nvidia inception logo

© All rights reserved
2021 made by Algoritmi Vision Inc.

If you believe that any of the summaries on our website lead to misinformation, don't hesitate to contact us. We will immediately review it and remove the summaries if necessary.

If your domain is listed as one of the sources on any summary, you can consider participating in the "Online Knowledge" program, if you want to proceed, please follow these instructions to apply.
However, if you still want us to remove all links leading to your domain from Plex.page and never use your website as a source, please follow these instructions.