Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, causing symmetric proximal muscle weakness. SMA is classified in three clinical types, SMA I, SMA II, and SMA III, based on the severity of the symptoms and the age of onset. About 95% of SMA cases are caused by homozygous deletion of the survival motor neuron 1 (SMN1) gene (5q13), or its conversion to SMN2. The molecular diagnosis of this disease is usually carried out by a polymerase chain reaction-restriction fragment length polymorphism approach able to evidence the absence of both SMN1 copies. However, this approach is not able to identify heterozygous healthy carriers, which show a very high frequency in general population (1:50). We used the multiple ligation-dependent probe amplification (MLPA) approach for the molecular diagnosis of SMA in 19 affected patient and in 57 individuals at risk to become healthy carriers. This analysis detected the absence of the homozygous SMN1 in all the investigated cases, and allowed to discriminate between SMN1 deletion and conversion to SMN2 on the basis of the size showed by the peaks specific for the different genes mapped within the SMA critical region. Moreover, MLPA analysis evidenced a condition of the absence of the heterozygous SMN1 in 33 out of the 57 relatives of the affected patients, demonstrating the usefulness of this approach in the identification of healthy carriers. Thus, the MLPA technique represents an easy, low cost, and high throughput system in the molecular diagnosis of SMA, both in affected patients and in healthy carriers.
| Original language | English |
|---|---|
| Pages (from-to) | 269-276 |
| Number of pages | 8 |
| Journal | Neurogenetics |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 2006 |
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Keywords
- MLPA
- SMN1
- SMN2
- Spinal muscular atrophy (SMA)
ASJC Scopus subject areas
- Genetics(clinical)
- Neuroscience(all)
Cite this
Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification. / Scarciolla, Oronzo; Stuppia, Liborio; De Angelis, Maria Vittoria; Murru, Stefania; Palka, Chiara; Giuliani, Rossella; Pace, Marta; Di Muzio, Antonio; Torrente, Isabella; Morella, Annunziata; Grammatico, Paola; Giacanelli, Manlio; Rosatelli, Maria Cristina; Uncini, Antonino; Dallapiccola, Bruno.
In: Neurogenetics, Vol. 7, No. 4, 11.2006, p. 269-276.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification
AU - Scarciolla, Oronzo
AU - Stuppia, Liborio
AU - De Angelis, Maria Vittoria
AU - Murru, Stefania
AU - Palka, Chiara
AU - Giuliani, Rossella
AU - Pace, Marta
AU - Di Muzio, Antonio
AU - Torrente, Isabella
AU - Morella, Annunziata
AU - Grammatico, Paola
AU - Giacanelli, Manlio
AU - Rosatelli, Maria Cristina
AU - Uncini, Antonino
AU - Dallapiccola, Bruno
PY - 2006/11
Y1 - 2006/11
N2 - Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, causing symmetric proximal muscle weakness. SMA is classified in three clinical types, SMA I, SMA II, and SMA III, based on the severity of the symptoms and the age of onset. About 95% of SMA cases are caused by homozygous deletion of the survival motor neuron 1 (SMN1) gene (5q13), or its conversion to SMN2. The molecular diagnosis of this disease is usually carried out by a polymerase chain reaction-restriction fragment length polymorphism approach able to evidence the absence of both SMN1 copies. However, this approach is not able to identify heterozygous healthy carriers, which show a very high frequency in general population (1:50). We used the multiple ligation-dependent probe amplification (MLPA) approach for the molecular diagnosis of SMA in 19 affected patient and in 57 individuals at risk to become healthy carriers. This analysis detected the absence of the homozygous SMN1 in all the investigated cases, and allowed to discriminate between SMN1 deletion and conversion to SMN2 on the basis of the size showed by the peaks specific for the different genes mapped within the SMA critical region. Moreover, MLPA analysis evidenced a condition of the absence of the heterozygous SMN1 in 33 out of the 57 relatives of the affected patients, demonstrating the usefulness of this approach in the identification of healthy carriers. Thus, the MLPA technique represents an easy, low cost, and high throughput system in the molecular diagnosis of SMA, both in affected patients and in healthy carriers.
AB - Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, causing symmetric proximal muscle weakness. SMA is classified in three clinical types, SMA I, SMA II, and SMA III, based on the severity of the symptoms and the age of onset. About 95% of SMA cases are caused by homozygous deletion of the survival motor neuron 1 (SMN1) gene (5q13), or its conversion to SMN2. The molecular diagnosis of this disease is usually carried out by a polymerase chain reaction-restriction fragment length polymorphism approach able to evidence the absence of both SMN1 copies. However, this approach is not able to identify heterozygous healthy carriers, which show a very high frequency in general population (1:50). We used the multiple ligation-dependent probe amplification (MLPA) approach for the molecular diagnosis of SMA in 19 affected patient and in 57 individuals at risk to become healthy carriers. This analysis detected the absence of the homozygous SMN1 in all the investigated cases, and allowed to discriminate between SMN1 deletion and conversion to SMN2 on the basis of the size showed by the peaks specific for the different genes mapped within the SMA critical region. Moreover, MLPA analysis evidenced a condition of the absence of the heterozygous SMN1 in 33 out of the 57 relatives of the affected patients, demonstrating the usefulness of this approach in the identification of healthy carriers. Thus, the MLPA technique represents an easy, low cost, and high throughput system in the molecular diagnosis of SMA, both in affected patients and in healthy carriers.
KW - MLPA
KW - SMN1
KW - SMN2
KW - Spinal muscular atrophy (SMA)
UR - http://www.scopus.com/inward/record.url?scp=33750069739&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750069739&partnerID=8YFLogxK
U2 - 10.1007/s10048-006-0051-3
DO - 10.1007/s10048-006-0051-3
M3 - Article
VL - 7
SP - 269
EP - 276
JO - Neurogenetics
JF - Neurogenetics
SN - 1364-6745
IS - 4
ER -