title: Prenatal prediction of spinal muscular atrophy. Experience with linkage studies and consequences of present SMN deletion analysis.
abstract: With the localisation of the gene for the autosomal recessive forms of proximal spinal muscular atrophies (SMA) to the chromosomal region 5q13 and the later detection of homozygous deletions of the SMN gene located in this region, prenatal prediction of SMA has become feasible and is widely applied now. In our experience with 77 prenatal predictions of SMA, follow-up of the 39 liveborn children from these pregnancies never led to a false-negative result. Application of SMN deletion analysis has consequences for prenatal prediction of SMA. When the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal prediction and interpretation of results are straightforward. In families in which no DNA from the index patient is available, prenatal detection of a homozygous SMN deletion may be considered almost proof of SMA in the fetus. Absence of a deletion, however, will not guarantee an unaffected child. A real problem exists if the index patient does not show a homozygous deletion of SMN exon 7. In such cases with non-homozygous SMN deletions, one cannot be certain of 5q linkage and autosomal recessive inheritance until other SMN mutations are detected. This is an argument to abstain from prenatal diagnosis by linkage analysis in these families.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Cobben
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: M
authors.initials: M
authors.lastname: De Visser
authors.forename: G
authors.initials: G
authors.lastname: Van der Steege
authors.forename: J B
authors.initials: JB
authors.lastname: Verhey
authors.forename: J
authors.initials: J
authors.lastname: Osinga
authors.forename: M
authors.initials: M
authors.lastname: Burton
authors.forename: R G
authors.initials: RG
authors.lastname: Mensink
authors.forename: P M
authors.initials: PM
authors.lastname: Grootscholten
authors.forename: L P
authors.initials: LP
authors.lastname: Ten Kate
authors.forename: C H
authors.initials: CH
authors.lastname: Buys
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009426:Netherlands; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017384:Sequence Deletion
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins