UNUSUAL MOLECULAR FINDINGS IN AUTOSOMAL RECESSIVE SPINAL MUSCULAR-ATROPHY

All three types of autosomal recessive spinal muscular atrophy map to chromosome 5q11.2-q13.3 and are associated with deletions or mutations of the SMN (survival motor neurone) gene. The availability of a test to distinguish between the SMN gene and its nearly identical centromer ic copy (C)BCD541 allows molecular diagnosis. We have analysed patient s from 24 Belgian and 34 Turkish families for the presence or absence of a deletion in the SMN gene. A homozygous deletion in the SMN gene w as seen in 90% of unrelated SMA patients. A non-radioactive SSCP assay allows for a semiquantitative analysis of the copy number of the cent romeric and SMN genes. Hence, direct carrier detection has become feas ible under certain conditions. We observed a phenotypically normal mal e, father of an SMA type I patient, presenting with only a single copy of the SMN gene and lacking both copies of the (C)BCD541 gene. This i llustrates that a reduction of the total number of SMN and (C)BCD541 g enes to a single SMN copy is compatible with normal life. In another S MA type I family, there is evidence for a de novo deletion of the cent romeric gene in a normal sib. This observation illustrates the suscept ibility of the SMA locus to de novo deletions and rearrangements.