title: Transmission ratio distortion in the spinal muscular atrophy locus: data from 314 prenatal tests.
abstract: BACKGROUND
  Spinal muscular atrophy (SMA) is a recessive neurodegenerative disorder characterized by the loss of alpha-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 chi2 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.
authors.affiliation: Department of Biopathology, Tor Vergata University of Rome, Rome, Italy. abottait@yahoo.it
authors.forename: A
authors.initials: A
authors.lastname: Botta
authors.forename: A
authors.initials: A
authors.lastname: Tacconelli
authors.forename: I
authors.initials: I
authors.lastname: Bagni
authors.forename: E
authors.initials: E
authors.lastname: Giardina
authors.forename: E
authors.initials: E
authors.lastname: Bonifazi
authors.forename: A
authors.initials: A
authors.lastname: Pietropolli
authors.forename: M
authors.initials: M
authors.lastname: Clementi
authors.forename: G
authors.initials: G
authors.lastname: Novelli
mesh_terms: D015193:Chorionic Villi Sampling; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein