Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population

Bueno, Keity C.; Gouvea, Silmara P.; Genari, Adriana Borges; Funayama, Carolina Araújo Rodrigues; Zanette, Dalila Lucíola; Silva, W.A.; Oliveira, Adriana Borges; Scola, Rosana Hermínia; Werneck, L.; Marques, Wilson

doi:10.1159/000324156

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…A recent Iranian registry showed a rate of 52.4% of consanguinity [18]. This low consanguinity rate in our population alerts us to a possible high prevalence of asymptomatic carriers for SMN1 deletion, which should be in the order of 1 to 37 persons, as reported by other studies in the Brazilian population [19]. The high recurrence rate of type 3 SMA (around 25%) was similar to that reported by a recent Iranian registry [18].…”

Section: Discussionsupporting

confidence: 88%

A self-reported Brazilian registry of spinal muscular atrophy: data from natural history, genetic characteristics, and multidisciplinary care

Mendonca,

de Godoi,

Zanoteli

2023

Preprint

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Background. Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. This study is intended to describe the key demographic, clinical and genetic characteristics, and natural history data of patients with SMA registered through a self-reported survey by patients or their parents. Results. By January 2022, 706 patients with 5q SMA had completed the questionnaire and had confirmatory molecular testing. Most patients reported having type 1 SMA (42%); 33% had type 2 SMA, and 23% had type 3 SMA. Six hundred sixty-seven patients (94.4%) had a homozygous SMN1-exon 7 deletion. One hundred thirty-one (18.6%) patients had a previous family history, and the familial recurrence rate was higher in patients with type 3 SMA, at 25.6%. The consanguinity rate was 5.2% in the studied population. Type 1 patients had a mean age of 3 months at the onset of symptoms and a delay of more than 3 months until genetic diagnosis. The median survival of patients with type 1 SMA without invasive ventilation was 27 months. Before 2018, the median age at the endpoint was 16 months, and after 2018, most patients (71%) were not submitted to invasive ventilation. About 50% of patients with type 3 SMA lost their walking ability by 37 years of age. Three hundred eighty-four (54.4%) patients claimed to have had access to some disease-modifying therapy, and 62.3% of type 1 patients were in treatment, while only 47.2% of type 2 SMA patients and 31.9% of type 3 SMA patients were in treatment. Conclusions. This is the first Brazilian registry of SMA and evidenced the accuracy and reliability of patient-reported data compared to previous studies. There is still a substantial diagnostic delay, especially in those patients with types 2 and 3 SMA. However, the study demonstrated prolonged survival, especially in type 1 patients.

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Section: Discussionsupporting

confidence: 88%

A self-reported Brazilian registry of spinal muscular atrophy: data from natural history, genetic characteristics, and multidisciplinary care

Mendonca,

de Godoi,

Zanoteli

2023

Preprint

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“…One of the 49 studied control subjects had 1 copy of the gene, being thus a carrier of the deletion. This corresponds to an allelic frequency of 0.01 in this sample (n = 98 chromosomes), for a carrier frequency of 2.04% (1/ 49) in the Venezuelan populations, being close to those values reported in diverse populations: Brazil 2.7% [18]; USA Caucasoids 2.7%; African Americans 1.1%; Ashkenazi Jews 2.2%; and 1.8% in Asians [19]. In sub-Saharan populations, the frequencies are lower: 1.6% in Nigerians, 0.83% in Kenyans, 0.48% in Malian [20]; in France, it is 2.9% in the general population [21].…”

Section: Gene Dosagessupporting

confidence: 88%

Spinal muscular atrophy in Venezuela: quantitative analysis of SMN1 and SMN2 genes

Yépez

Paradisi

Arias

2020

Egypt J Med Hum Genet

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Background: Spinal muscular atrophy (SMA) is mostly caused by homozygous deletions in the survival motor neuron 1 (SMN1) gene. SMN2, its paralogous gene, is a genetic modifier of the disease phenotype, and its copy number is correlated with SMA severity. The purpose of the study was to investigate the number of copies of the SMN1 and SMN2 genes in a Venezuelan population control sample and in patients with a presumptive diagnosis of SMA, besides estimating the frequency of mutation carriers in the population. Results: SMN1 and SMN2 gene copies were assessed in 49 Venezuelan dweller unrelated normal individuals and in 94 subjects from 29 families with a SMA presumptive diagnosis, using the quantitative PCR method. A SMN1 deletion carrier frequency of 0.01 and 0.163 of homozygous absence of the SMN2 gene were found in the Venezuelan control sample. Deletion of SMN1 exon 7 was confirmed in 15 families; the remaining 14 index cases had two SMN1 copies and a heterogeneous phenotype not attributable to SMN deletions. Based on clinical features of the index cases and the SMN2 copy number, a positive phenotype-genotype correlation was demonstrated. No disease geographical aggregation was found in the country. Conclusion: The frequency of carriers of the deletion of exon 7 in SMN1 in the Venezuelan control population was similar to that observed in populations worldwide, while the frequency of 0 copies of the SMN2 gene (16.3 %) seems to be relatively high. All these findings have pertinent implications for the diagnosis and genetic counseling on SMA in Venezuela.

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“…The carrier frequency of genetic alterations in the SMN1 varies among different populations, from 1 in 38 to 1 in 72. 7,8 The SMN2 differs from SMN1 by a single nucleotide variant (840C ! T) in exon 7, resulting in the loss of exon 7 from most transcripts during messenger RNA processing, leading to the translation of a truncated and unstable SMN protein.…”

Section: Introductionmentioning

confidence: 99%

“…The carrier frequency of genetic alterations in the SMN1 varies among different populations, from 1 in 38 to 1 in 72. 7 8 …”

Section: Introductionmentioning

confidence: 99%

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

Zanoteli,

Araujo,

Becker

et al. 2024

Arq Neuropsiquiatr

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Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes.

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Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population

Cited by 7 publications

References 55 publications

A self-reported Brazilian registry of spinal muscular atrophy: data from natural history, genetic characteristics, and multidisciplinary care

A self-reported Brazilian registry of spinal muscular atrophy: data from natural history, genetic characteristics, and multidisciplinary care

Spinal muscular atrophy in Venezuela: quantitative analysis of SMN1 and SMN2 genes

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

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