Phenotype variability in patients with infantile spinal muscular atrophy: Distal muscle weakness and peripheral neuropathy in compound heterozygotes with SMN1 gene deletions

Spinal Muscular Atrophy (SMA) is the second leading genetic disorder inherited in the autosomal recessive pattern due to the absence of the SMN1 gene characterized by loss of motor neurons and progressive muscle wasting, often leading to dependent life and decreased life span. In Ayurveda, this condition can be considered as Kulaja Vyadhi wherein the patient’s Mamsa and Snayu is affected by Vata. This can be regarded as Mamsa-Snayugata Sarvanga Vata. It is said that Prakruta Vata dosha is the life, it is the strength, it is the sustainer of the body, it holds the body and life together. If it is Vikruta it produces Sankocha, Khanja, Kubjatva, Pangutva, Khalli and Soshana of Anga. So, in this disease aggravated Vata does the vitiation of Mamsa and Snayu thus leading to Soshana of both, resulting in Stambha, Nischalikarana of Avayava. A 21years female patient was admitted to our I.P.D with c/o of reduced strength in all four limbs leading to the inability to walk and to maintain erect posture during standing and sitting positions. Based on Ayurvedic principles the patient was initially subjected to Avaranahara Chikitsa followed by Brimhana line of management. Keywords: Mamsagata vata, Snayugata vata, Sarvanga vata, Spinal muscular atrophy (SMA)

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Constraints of carrier screening in spinal muscular atrophy: Co-existence of deletion and duplication in SMN1 gene and false negative MLPA result

Gene Reports ◽

10.1016/j.genrep.2019.100440 ◽

2019 ◽

Vol 16 ◽

pp. 100440

Author(s):

Zohreh Sharifi ◽

Flora Forouzesh ◽

Mohammad Taheri ◽

Sirous Zeinali

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

False Negative ◽

Carrier Screening ◽

Smn1 Gene

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Validation of a Fast, Robust, Inexpensive, Two-Tiered Neonatal Screening Test algorithm on Dried Blood Spots for Spinal Muscular Atrophy

International Journal of Neonatal Screening ◽

10.3390/ijns5020021 ◽

2019 ◽

Vol 5 (2) ◽

pp. 21 ◽

Cited By ~ 3

Author(s):

Annuska Strunk ◽

Andre Abbes ◽

Antoine Stuitje ◽

Chris Hettinga ◽

Eline Sepers ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Newborn Screening ◽

Neonatal Screening ◽

Muscular Atrophy ◽

Melting Curve ◽

Curve Analysis ◽

Melting Curve Analysis ◽

Smn1 Gene ◽

Screening Programs ◽

Crude Extracts

Spinal muscular atrophy (SMA) is one of the leading genetic causes of infant mortality with an incidence of 1:10,000. The recently-introduced antisense oligonucleotide treatment improves the outcome of this disease, in particular when applied at an early stage of progression. The genetic cause of SMA is, in >95% of cases, a homozygous deletion of the survival motor neuron 1 (SMN1) gene, which makes the low-cost detection of SMA cases as part of newborn screening programs feasible. We developed and validated a new SALSA MC002 melting curve assay that detects the absence of the SMN1 exon 7 DNA sequence without detecting asymptomatic carriers and reliably discriminates SMN1 from its genetic homolog SMN2 using crude extracts from newborn screening cards. Melting curve analysis shows peaks specific for both the SMN1 gene and the disease modifying SMN2 homolog. The detection of the SMN2 homolog, of which the only clinically relevant difference from the SMN1 gene is a single nucleotide in exon 7, was only used to confirm a correct reaction in samples that lacked the SMN1 gene, and not for SMN2 quantification. We retrieved 47 DBS samples from children with genetically-confirmed SMA, after informed consent from parents, and 375 controls from the national archive of the Dutch National Institute for Public Health and the Environment (RIVM). The assay correctly identified all anonymized and randomized SMA and control samples (i.e., sensitivity and specificity of 100%), without the detection of carriers, on the three most commonly-used PCR platforms with melting curve analysis. This test’s concordance with the second-tier ‘golden standard’ P021 SMA MLPA test was 100%. Using the new P021–B1 version, crude extracts from DBS cards could also be used to determine the SMN2 copy number of SMA patients with a high level of accuracy. The MC002 test showed the feasibility and accuracy of SMA screening in a neonatal screening program.

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SMN1 gene point mutations in type I–IV proximal spinal muscular atrophy patients with a single copy of SMN1

Russian Journal of Genetics ◽

10.1134/s1022795415080128 ◽

2015 ◽

Vol 51 (9) ◽

pp. 925-931

Author(s):

V. V. Zabnenkova ◽

E. L. Dadali ◽

S. B. Artemieva ◽

I. V. Sharkova ◽

G. E. Rudenskaya ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Point Mutations ◽

Single Copy ◽

Type I ◽

Smn1 Gene ◽

Proximal Spinal Muscular Atrophy

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Distrubances of neuromuscular interaction may contribute to muscle weakness in spinal muscular atrophy

Neuromuscular Disorders ◽

10.1016/s0960-8966(97)00047-3 ◽

1997 ◽

Vol 7 (6-7) ◽

pp. 369-372 ◽

Cited By ~ 12

Author(s):

Linda Greensmith ◽

Gerta Vrbová

Keyword(s):

Spinal Muscular Atrophy ◽

Muscle Weakness ◽

Muscular Atrophy

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Clinical features and genetics in non-5q spinal muscular atrophy caused by acid ceramidase deficiency

Journal of Medicine and Life ◽

10.25122/jml-2021-0147 ◽

2021 ◽

Vol 14 (3) ◽

pp. 424-428

Author(s):

Mihaela Axente ◽

◽

Elena-Silvia Shelby ◽

Andrada Mirea ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Smn1 Gene ◽

Progressive Degeneration ◽

Whole Exome ◽

Uncertain Significance ◽

Progressive Myoclonic Epilepsy ◽

Ceramidase Deficiency ◽

Next Generation Sequencing Ngs

Spinal muscular atrophy (SMA) is a spectrum of genetically and clinically heterogeneous diseases leading to the progressive degeneration of peripheric motor neurons with subsequent muscle weakness and atrophy. More than 95% of the cases of SMA are represented by homozygous mutations of the SMN1 gene (5q-SMA). Because this disease represents the leading cause of death due to a genetic cause and due to the availability of genetic therapies which can now save the life of the patient and stop the progress of the disease, early diagnosis is crucial. This report presents the case of a 13-year-old patient admitted to our hospital in 2018 who presented a phenotype typical to 5q-SMA. Next-generation sequencing (NGS) and Sanger sequencing of the SMN1 gene were performed, and a negative result was obtained. Consequently, we continued testing using whole-exome sequencing and discovered three mutations in the ASAH1 gene (one pathogenic and two variants of uncertain significance). Pathogenic mutations in the ASAH1 gene are responsible for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease, which overlapped with our patient’s phenotype. Currently, there are 45 SMA cases caused by mutations in the ASAH1 gene reported worldwide; however, the present case is the first reported in Romania.

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