PRENATAL PREDICTION OF SPINAL MUSCULAR-ATROPHY - EXPERIENCE WITH LINKAGE STUDIES AND CONSEQUENCES OF PRESENT SMN DELETION ANALYSIS

With the localisation of the gene for the autosomal recessive forms of proximal spinal muscular atrophies (SMA) to the chromosomal region 5q 13 and the later detection of homozygous deletions of the SMN gene loc ated in this region, prenatal prediction of SMA has become feasible an d is widely applied now. In our experience with 77 prenatal prediction s of SMA, follow-up of the 39 liveborn children from these pregnancies never led to a false-negative result. Application of SMN deletion ana lysis has consequences for prenatal prediction of SMA. When the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal pr ediction and interpretation of results are straightforward. In familie s in which no DNA from the index patient is available, prenatal detect ion of a homozygous SMN deletion may be considered almost proof of SMA in the fetus. Absence of a deletion, however, will not guarantee an u naffected child. A real problem exists if the index patient does not s how a homozygous deletion of SMN exon 7. In such cases with nonhomozyg ous SMN deletions, one cannot be certain of 5q linkage and autosomal r ecessive inheritance until other SMN mutations are detected. This is a n argument to abstain from prenatal diagnosis by linkage analysis in t hese families.