PRENATAL-DIAGNOSIS OF THE ACUTE FORM OF PROXIMAL SPINAL MUSCULAR-ATROPHY - EXPERIENCE ON THE ACCEPTANCE OF LINKAGE ANALYSES BY THE FAMILIES

The acute form of proximal spinal muscular atrophy (SMA) is a severe a utosomal recessive inherited neuromuscular disorder. It has been mappe d to chromosome 5q 11.2-13.3. Using restriction fragment length polymo rphisms (RFLPs) or (CA)n repeats of DNA probes in this region, prenata l diagnosis is, in principle, possible. Misdiagnosis can be due to inc orrect diagnosis in the index patient, and crossing-over events. Using the DNA probes D5S6, D5S112, D5S39, and D5S78, we cover a region of 1 0.4 mega-base pairs (Mbp) of partially NotI-digested genomic DNA witho ut overlap of fragments. The DNA probes D5S6 and D5S112, most likely f lanking the SMA gene, cover a distance of about 6.6 Mbp. This correspo nds to the genetic distance of 6 cM (Morrison et al., 1992; Daniels et al., 1992). But since the precise localization of the SMA gene is sti ll unknown (Simard et al., 1992), a 10 per cent risk of misdiagnoses d ue to crossing-over events cannot be excluded. The acceptance of this 10 percent risk for prenatal diagnoses differs in SMA families. We obs erved a case in which a woman accepted a 25 per cent risk because RFLP s and (CA). repeats were both uninformative. In contrast, another fami ly did not accept the minimal 10 per cent risk and the pregnancy was t erminated. In two families, we performed prenatal diagnosis by linkage analysis. One child predicted to be healthy has been born in the mean time and has shown no indication of SMA during her first 8 months.