A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

Shinohara, Masakazu; Niba, Emma Tabe Eko; Wijaya, Yogik Onky Silvana; Takayama, Izumi; Mitsuishi, Chisako; Kumasaka, Sakae; Kondo, Yoichi; Takatera, Akihiro; Hokuto, Isamu; Morioka, Ichiro; Ogiwara, Kazutaka; Tobita, Kimimasa; Takeuchi, Atsuko; Nishio, Hisahide

doi:10.3390/ijns5040041

Cited by 25 publications

(42 citation statements)

References 26 publications

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“…We have established a simple system using DBS for SMA newborn screening [13]. In this study, we aimed to establish another simple system using DBS to screen for SMA carrier status.…”

Section: Objectives and Ethicsmentioning

confidence: 99%

“…To detect SMN1 deletion, samples from Mongolian and Indonesian SMA patients and their parents were analyzed using the method of Shinohara et al [13]. Patient 1 was a 21-month-old boy who showed delayed motor milestones and muscle weakness.…”

Section: Dbs Samples From Mongolian and Indonesian Sma Familiesmentioning

confidence: 99%

“…We performed SMN1 deletion tests with DBS on FTA cards and Guthrie cards using the previously described procedures [13]. Our procedure outline was: (1) a punched DBS circle was placed directly into conventional PCR reaction mixture, followed by the pre-amplification of the SMN1/SMN2 exon 7-targeted region with 40 cycles (to reach the plateau phase in the first round PCR).…”

Section: Detection Of Homozygous Smn1 Deletion In Dbs Samplesmentioning

confidence: 99%

“…Several pilot studies have been reported that describe newborn screening for SMA using dried blood spots (DBS) on filter paper [9][10][11][12][13]. Vill et al stated, based on their experience of SMA newborn screening and presymptomatic treatment, that newborn screening improved the outcome for children with genetically proven SMA, and concluded that newborn screening for SMA should be introduced in all countries where therapy is available [14].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we developed a new simple, accurate, and inexpensive system for determining the SMN1 copy number and SMA carrier status. This system is, in a sense, a modified version of our system to detect the homozygous deletion of SMN1 [13]. Our current system, which uses a dried blood spot (DBS) on filter paper, may provide critical information to SMA families all over the world.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Spinal Muscular Atrophy Carrier Status by Determining SMN1 Copy Number Using Dried Blood Spots

Wijaya

Purevsuren

Harahap

et al. 2020

IJNS

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Spinal muscular atrophy (SMA) is a common neuromuscular disease with autosomal recessive inheritance. The disease gene, SMN1, is homozygously deleted in 95% of SMA patients. Although SMA has been an incurable disease, treatment in infancy with newly developed drugs has dramatically improved the disease severity. Thus, there is a strong rationale for newborn and carrier screening for SMA, although implementing SMA carrier screening in the general population is controversial. We previously developed a simple, accurate newborn SMA screening system to detect homozygous SMN1 deletions using dried blood spots (DBS) on filter paper. Here, we modified our previous system to detect the heterozygous deletions of SMN1, which indicates SMA carrier status. The system involves a calibrator-normalized relative quantification method using quantitative nested PCR technology. Our system clearly separated the DBS samples with one SMN1 copy (carrier status with a heterozygous deletion of SMN1) from the DBS samples with two SMN1 copies (non-carrier status with no deletion of SMN1). We also analyzed DBS samples from SMA families, confirmed SMA in the affected children, and determined the carrier status of their parents based on the SMN1 copy number. In conclusion, our system will provide essential information for risk assessment and genetic counseling, at least for SMA families.

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“…We have established a simple system using DBS for SMA newborn screening [13]. In this study, we aimed to establish another simple system using DBS to screen for SMA carrier status.…”

Section: Objectives and Ethicsmentioning

confidence: 99%

Section: Dbs Samples From Mongolian and Indonesian Sma Familiesmentioning

confidence: 99%

Section: Detection Of Homozygous Smn1 Deletion In Dbs Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Assessment of Spinal Muscular Atrophy Carrier Status by Determining SMN1 Copy Number Using Dried Blood Spots

Wijaya

Purevsuren

Harahap

et al. 2020

IJNS

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Early spinal muscular atrophy treatment following newborn screening: A 20‐month review of the first Italian regional experience

Gagliardi,

Canzio,

Orsini

et al. 2024

Ann Clin Transl Neurol

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ObjectivesMandatory newborn screening (NBS) for spinal muscular atrophy (SMA) was implemented for the first time in Italy at the end of 2021, allowing the identification and treatment of patients at an asymptomatic stage.MethodsDNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real‐time PCR‐based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment.ResultsOver the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow‐up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days.InterpretationThe timely administration of disease‐modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale.

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A new line method; A direct test in spinal muscular atrophy screening for DBS

Kubar,

Temel,

Beken

et al. 2023

Molec Gen & Gen Med

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BackgroundNucleic acid‐based assays provide an opportunity to screen for genetically encoded diseases like spinal muscular atrophy (SMA), before the onset of symptoms. Nowadays, such assays could be easily utilized as high‐throughputs in SMA to detect a homozygous deletion of exon 7 of the survival motor neuron 1 gene (SMN1) that is responsible for >95% of SMA patients.MethodsWe developed a new line method (NLM) as a direct real time PCR test procedure without nucleic acid extraction in dried blood spots (DBS) to screen for homozygous deletion of exon 7 of the SMN1 gene. Performance of this setup was evaluated on 580 DBS newborn samples and air dried 50 DBS from whole blood including 20 samples for homozygous deletion of the SMN1 gene detected earlier with MLPA.ResultsWe found all 580 newborn DBS samples as wild type. DBS prepared from 50 whole blood samples also including 20 affected people were correctly identified as homozygous deletions and 30 wild types of exon 7 of SMN1 as before with MLPA. When the MLPA method was taken as the gold standard, the sensitivity and specificity of the NLM test were found 100% for the detection of SMN1 exon 7 homozygous deletion.ConclusionIn the NLM, the total test duration has been reduced to less than 75 min without requiring any extra process such as DNA extraction step and sample plate preparation after the punching step. Thereby, newborn SMA screening with the NLM has gained an environmentally friendly feature with not requiring additional tedious steps.

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A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

Cited by 25 publications

References 26 publications

Assessment of Spinal Muscular Atrophy Carrier Status by Determining SMN1 Copy Number Using Dried Blood Spots

Assessment of Spinal Muscular Atrophy Carrier Status by Determining SMN1 Copy Number Using Dried Blood Spots

Early spinal muscular atrophy treatment following newborn screening: A 20‐month review of the first Italian regional experience

A new line method; A direct test in spinal muscular atrophy screening for DBS

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