Prenatal diagnosis for risk of spinal muscular atrophy.
OBJECTIVE
Prenatal diagnosis of spinal muscular atrophy is usually performed in high risk couples by detection of a homozygous deletion in the survival motor neurone gene (SMN1). However, other relatives at risk of being carriers very often request genetic counselling and the possibility of prenatal diagnosis. The aim of this study was to validate a SMN1 gene quantitative test to help the couples formed by one spinal muscular atrophy carrier and a partner of the general population (1/200 potential risk) to achieve a less ambiguous risk result for the pregnancy.


METHODS
Spinal muscular atrophy carrier studies in at-risk individuals.


METHODS
Department of Genetics and Gynaecology and Obstetrics in a large university hospital.


METHODS
Seventy-nine obligate carriers (more than one affected child with deletion in the offspring) and 58 non-carriers (relatives of spinal muscular atrophy families defined by marker studies) were tested to set up a quantitative analysis. The method was applied in different situations in 126 members from 34 families with spinal muscular atrophy patients.


METHODS
DNA studies of the SMNI gene by marker analysis and quantitative assay.


METHODS
To determine double (non-carrier) or single dose (carrier) of exon 7 of the SMN1 gene in relatives of spinal muscular atrophy patients. Bayesian calculation of risk.


RESULTS
The sensitivity and specificity of the method were 96% and 100%, respectively. Studies on different couples with an a priori risk of 1/200 allowed us to reduce the final risk to 1/5000 or to increase it to 1/4.


CONCLUSIONS
The quantitative method can be used to achieve a less ambiguous risk in pregnancies with a 1/200 risk and in families where no sample is available to study the index case. Screening of gamete donors when the recipient is a known carrier should also be considered.
Cuscó
I
I
Genetics and Research Institute, Hospital de Sant Pau, Barcelona, Spain.
Barceló
M J
MJ
Soler
C
C
Parra
J
J
Baiget
M
M
Tizzano
E
E
D017362:Cyclic AMP Response Element-Binding Protein; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D005820:Genetic Testing / Q000379:methods*; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016601:RNA-Binding Proteins; D012307:Risk Factors; D055532:SMN Complex Proteins; D012680:Sensitivity and Specificity; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis* / Q000235:genetics; D055533:Survival of Motor Neuron 1 Protein
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