Intragenic variants in the SMN1 gene determine the clinical phenotype in 5q spinal muscular atrophy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Mendonça Rodrigo de Holanda, Matsui Ciro, Polido Graziela Jorge, Silva André Macedo Serafim, Kulikowski Leslie, Torchio Dias Alexandre, Zanardo Evelin Aline, Solla Davi Jorge Fontoura, Gurgel-Giannetti Juliana, de Moura Ana Carolina Monteiro Lessa, Sampaio Gabriela Palhares Campolina, Oliveira Acary Souza Bulle, de Souza Paulo Victor Sgobbi, Pinto Wladimir Bocca Vieira de Rezende, Gonçalves Eduardo Augusto, Farias Igor Braga, Nardes Flávia, Araújo Alexandra Prufer de Queiroz Campos, Marques Wilson, Tomaselli Pedro José, Ribeiro Mara Dell Ospedale, Kitajima João Paulo, Paoli Monteiro Fabíola, Saute Jonas Alex Morales, Becker Michele Michelin, Saraiva-Pereira Maria Luiza, Brusius-Facchin Ana Carolina, van der Linden Vanessa, Florêncio Rodrigo Neves, Barbosa André Vinícius Soares, Machado-Costa Marcela Camara, Pessoa André Luiz Santos, Souza Leticia Silva, Franca Marcondes Cavalcante, Kok Fernando, Reed Umbertina Conti, Zanoteli Edmar
Аннотация
METHODS: Four hundred fifty Brazilian patients with SMA were included in a retrospective study, and clinical data were analyzed compared with genetic data; the SMN2 copy number was obtained by multiplex ligation-dependent probe amplification and pathogenic variants in SMN1 by next-generation sequencing.
RESULTS: Four hundred two patients (89.3%) presented homozygous exon 7-SMN1 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 SMN2 copy number, whereas the variants c.460C>T and c.5C>G determined a milder phenotype independently of the SMN2 copies.
CONCLUSIONS: Patients with specific pathogenic variants (c.460C>T and c.5C>G) presented a milder phenotype, and the SMN2 copy number did not correlate with disease severity in this group.