Sofía Medrano1, Soledad Monges2, Luis Pablo Gravina1, Laura Alías3, Julieta Mozzoni4, Hilda Verónica Aráoz1, Sara Bernal3, Angélica Moresco5, Lilien Chertkoff1, Eduardo Tizzano6. 1. Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina. 2. Servicio de Neurología, Hospital de Pediatría Garrahan, Buenos Aires, Argentina. 3. Servicio de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBERER U-705, Barcelona, Spain. 4. Servicio de Kinesiología, Hospital de Pediatría Garrahan, Buenos Aires, Argentina. 5. Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina. 6. Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Barcelona, Spain; CIBERER U-705, Barcelona, Spain. Electronic address: etizzano@vhebron.net.
Abstract
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.
BACKGROUND/ PURPOSE:Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, considered one of the leading causes of infantmortality. 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.
Authors: Anna Lusakowska; Maria Jedrzejowska; Anna Kaminska; Katarzyna Janiszewska; Przemysław Grochowski; Janusz Zimowski; Janusz Sierdzinski; Anna Kostera-Pruszczyk Journal: Orphanet J Rare Dis Date: 2021-03-24 Impact factor: 4.123