Transmission ratio distortion in the spinal muscular atrophy locus: Data from 314 prenatal tests

Autor: Maurizio Clementi, Emiliano Giardina, Ilaria Bagni, Emanuela Bonifazi, Giuseppe Novelli, Adalgisa Pietropolli, Alessandra Tacconelli, A. Botta
Jazyk: angličtina
Rok vydání: 2005
Předmět:
survival motor neuron protein
DNA Mutational Analysis
Inheritance Patterns
SMN1
Gene mutation
Gene Frequency
Pregnancy
Prenatal Diagnosis
gene mutation
Cyclic AMP Response Element-Binding Protein
spinal muscular atrophy
Genetics
Genetic Screening
Homozygote
allele
article
Chromosome Mapping
RNA-Binding Proteins
SMN Complex Proteins
SMA
fetus
Muscular Atrophy
heterozygote detection
priority journal
risk factor
Chorionic Villi Sampling
symbols
Chromosomes
Human
Pair 5
Female
wild type
Pair 5
chorion villus sampling
Heterozygote
Genotype
Spinal
controlled study
human
linkage analysis
major clinical study
prenatal screening
statistical analysis
Gene Deletion
Genes
Recessive
Genetic Counseling
Genetic Predisposition to Disease
Humans
Microsatellite Repeats
Muscular Atrophy
Spinal
Mutation
Nerve Tissue Proteins
Locus (genetics)
Prenatal diagnosis
Biology
Chromosomes
symbols.namesake
medicine
Recessive
Genetic Testing
Allele
Spinal muscular atrophy
medicine.disease
Survival of Motor Neuron 1 Protein
Genes
Settore MED/03 - Genetica Medica
Mendelian inheritance
Neurology (clinical)
Popis: Background: Spinal muscular atrophy (SMA) is a recessive neurodegenerative disorder characterized by the loss of α-motor neurons in the spinal cord and subsequent death of motor neuron cells. SMA occurs with a frequency of 1 in 6,000 live births, with a carrier frequency of 1 in 40, and is a leading genetic cause of infant mortality. SMA is caused by loss or mutation of the telomeric survival motor neuron gene ( SMN1 ), which is deleted in almost 94% of SMA patients Objective: To analyze the transmission ratio at the SMA locus, examining the segregation of the SMN1 -deleted alleles in 314 fetuses from carrier parents who requested prenatal testing for the disease. Methods: Prenatal diagnosis of SMA in families at 25% risk of the disease has been performed on chorionic villous sampling specimens, through direct detection of the SMN1 gene mutation and linkage analysis using microsatellite markers from the 5q13 region. Analysis of the genotypic/allelic frequencies of the SMN1 gene was performed using the χ 2 test, assuming a recessive mendelian inheritance. Results: Of 314 fetuses analyzed, 95 were homozygous for the wild-type allele (30.3%), 154 were carriers (49.0%), and the remaining 65 were homozygous for the mutated allele (20.7%). Statistical analysis demonstrated that proportion of fetuses predicted with SMA is lower than 25% expected for a recessive disorder, resulting in a transmission rate of the SMN1 -deleted allele deviant from the 50% expected in a random the segregation of a mendelian tract ( p = 0.016) Conclusions: This is the first study to evaluate the genotypic frequencies at the spinal muscular atrophy (SMA) locus based on data derived from prenatal analysis, which are not subject to ascertainment bias. The analysis showed a transmission ratio distortion at the SMA locus in favor of the SMN1 wild-type alleles.
Databáze: OpenAIRE
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