Genotype–phenotype correlation of SMN locus genes in spinal muscular atrophy children from Argentina

Authors
Medrano, Sofía; Monges, Soledad; Gravina, Luis Pablo; Alías, Laura; Mozzoni, Julieta; Aráoz, Hilda Verónica; Bernal, Sara; Moresco, Angélica; Chertkoff, Lilien Patricia; Tizzano, Eduardo
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
Background/Purpose: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, considered one of the leading causes of infant mortality. It is caused by mutations in the SMN1 gene. A highly homologous copy of this gene named SMN2 and other neighbouring genes, SERF1A and NAIP, are considered phenotypic modifiers of the disease. In recent years, notable advances have been made in SMA research regarding evaluation, prognosis, and therapeutic options. Thus, genotype-phenotype studies in SMA are important to stratify patients for motor function tests and for envisaged clinical trials. The aim of this study was to provide clinical and molecular data of a series of Argentinean children with SMA to establish a comprehensive genotype-phenotype correlation. Methods: 144 Argentinean children with SMA (56 children with type I, 58 with type II, and 30 with type III) were evaluated. The copy number of SMN2, SERF1A, and NAIP genes was established using MLPA (Multiplex Ligation-dependent Probe Amplification) and then correlated with the patients clinical subtypes. To improve clinical characterization we considered the initial symptoms that prompted the consultation, age of acquisition of motor abilities to independent walking and age at loss of gait. We also evaluated clinical and molecular features of sibling pairs in seven families. Results: A strong correlation was observed between the SMN2 copy number and SMA phenotype while SERF1A and NAIP copy number showed a moderate correlation. We observed intra- and inter-family differences among the SMA types. Conclusion: This first genotype-phenotype correlation study in Argentinean SMA children provides data to improve patient stratification and define more adequate follow-up parameters.
Fil: Medrano, Sofía. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Monges, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gravina, Luis Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Alías, Laura. Hospital de la Santa Creu i Sant Pau; España. CIBERER; España
Fil: Mozzoni, Julieta. Hospital de la Santa Creu i Sant Pau; España
Fil: Aráoz, Hilda Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Bernal, Sara. Hospital de la Santa Creu i Sant Pau; España. CIBERER; España
Fil: Moresco, Angélica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Chertkoff, Lilien Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Tizzano, Eduardo. Hospital Valle Hebron; España. CIBERER; España
Subject
Spinal muscular atrophy (SMA)
Survival motor neuron 1 gene (SMN1)
Survival motor neuron 2 gene (SMN2)
Neuronal apoptosis inhibitory protein gene (NAIP)
Small EDRK-rich factor 1A (SERF1A)
Multiplex Ligation-dependent Probe Amplification (MLPA)
Inmunología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/46958