AI Article Synopsis
- The study aimed to analyze the genetic variations in the survival motor neuron 1 (SMN1) gene among Brazilian patients with spinal muscular atrophy (SMA) and to connect these variants with disease severity.
- Out of 450 patients, the majority (89.3%) had a common deletion in exon 7, while others had a mix of this deletion and additional point mutations, with certain variants being more prevalent in compound heterozygous cases.
- The research concluded that specific variants (c.460C>T and c.5C>G) were linked to milder disease forms, and that the copy number of the gene did not consistently predict disease severity among these patients.*
Article Abstract
Objective: The aim of the study was to report the proportion of homozygous and compound heterozygous variants in the survival motor neuron 1 () gene in a large population of patients with spinal muscular atrophy (SMA) and to correlate the severity of the disease with the presence of specific intragenic variants in and with the copy number.
Methods: Four hundred fifty Brazilian patients with SMA were included in a retrospective study, and clinical data were analyzed compared with genetic data; the copy number was obtained by multiplex ligation-dependent probe amplification and pathogenic variants in by next-generation sequencing.
Results: Four hundred two patients (89.3%) presented homozygous exon 7- deletion, and 48 (10.7%) were compound heterozygous for the common deletion in one allele and a point mutation in the other allele. Recurrent variants in exons 3 and 6 (c.460C>T, c.770_780dup and c.734_735insC) accounted for almost 80% of compound heterozygous patients. Another recurrent pathogenic variant was c.5C>G at exon 1. Patients with c.770_780dup and c.734_735insC had a clinical phenotype correlated with copy number, whereas the variants c.460C>T and c.5C>G determined a milder phenotype independently of the copies.
Conclusions: Patients with specific pathogenic variants (c.460C>T and c.5C>G) presented a milder phenotype, and the copy number did not correlate with disease severity in this group.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524579 | PMC |
| http://dx.doi.org/10.1212/NXG.0000000000000505 | DOI Listing |
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