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Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China
Xiangdong Kong
Genetics and Prenatal diagnosis center，The First Affiliated Hospital of Zhengzhou University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-7638
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Medical Genetics.
Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.
Methods In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.
Results Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants.
Conclusions Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.
Keywords
Spinal muscular atrophy; SMN1 gene; MLPA; Long-range PCR; Prenatal diagnosis
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CURRENT STATUS: Published
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Posted 29 May, 2020
Published
On 18 Jun, 2020
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On 19 May, 2020
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Editorial decision: Minor revision
On 05 May, 2020
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Received 03 May, 2020
Reviewers invited
Invitations sent on 21 Apr, 2020
Reviewer #1 agreed
On 21 Apr, 2020
Editor assigned
On 16 Apr, 2020
Submission checks complete
On 15 Apr, 2020
Editor invited
On 15 Apr, 2020
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Review #1 received
Received 12 Mar, 2020
Editorial decision: Major revision
On 12 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Review #2 received
Received 09 Mar, 2020
Reviewer #1 agreed
On 01 Mar, 2020
Reviewers invited
Invitations sent on 29 Feb, 2020
Editor assigned
On 28 Feb, 2020
Submission checks complete
On 26 Feb, 2020
Editor invited
On 25 Feb, 2020
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This preprint is under consideration at BMC Medical Genetics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China
Xiangdong Kong
Genetics and Prenatal diagnosis center，The First Affiliated Hospital of Zhengzhou University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-7638
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 29 May, 2020
Published
On 18 Jun, 2020
No community comments so far
Editor assigned
On 19 May, 2020
Submission checks complete
On 18 May, 2020
Editor invited
On 18 May, 2020
No comments provided
Editorial decision: Minor revision
On 05 May, 2020
Review #1 received
Received 03 May, 2020
Reviewers invited
Invitations sent on 21 Apr, 2020
Reviewer #1 agreed
On 21 Apr, 2020
Editor assigned
On 16 Apr, 2020
Submission checks complete
On 15 Apr, 2020
Editor invited
On 15 Apr, 2020
No comments provided
Review #1 received
Received 12 Mar, 2020
Editorial decision: Major revision
On 12 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Review #2 received
Received 09 Mar, 2020
Reviewer #1 agreed
On 01 Mar, 2020
Reviewers invited
Invitations sent on 29 Feb, 2020
Editor assigned
On 28 Feb, 2020
Submission checks complete
On 26 Feb, 2020
Editor invited
On 25 Feb, 2020
First submitted
On 21 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medical Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Medical Genetics.
Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.
Methods In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.
Results Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants.
Conclusions Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.