When is a deletion not a deletion? When it is converted.

Proximal SMA is an autosomal recessive disorder that results in destruction of the motor neurons in the anterior horn of the spinal cord. SMA has an estimated incidence of 1/10,000 live births, with a carrier frequency of 1/40 (Pearn 1980). The childhood SMAs can be classified into three groups based on age at onset and clinical course. Type I SMA is the most severe form, with onset of symptoms before the age of 6 mo and with death occurring within the first 2 years of life. Type II SMA patients have an intermediate severity, with onset before age 18 mo and with patients never gaining the ability to walk. Type III SMA is the mildest form of this disease, with onset after the age of 18 mo and with patients achieving the ability to walk. All three forms of SMA have been mapped to 5q1213 (Brzustowicz et al. 1990; Melki et al. 1990; Simard et al. 1992; Francis et al. 1993; Brahe et al. 1994; Burghes et al. 1994a; Wirth et al. 1994, 1995a). In 1995, three papers reported different cDNAs (neuronal apoptosis inhibitory protein [NAIP] [Roy et al. 1995], survival motor neuron [SMN] [Lefebvre et al. 1995], and XS2G3 [XS2G3 is a segment of the NAIP gene] [Thompson et al. 1995]) that detect deletions in SMA patients. The NAIP and SMN genes are duplicated with a telomeric SMN (SMNT) and a centromeric SMN (SMNC), and NAIP is duplicated either with exon 5 (NAIP5) or without exon 5 (NAIPD). The NAIP5 gene was deleted in 50% of type I SMA patients, whereas the telomeric SMNT gene was deleted in 95% of patients of all severities (Cobben et al. 1995; Hahnen et al. 1995; Lefebvre et al. 1995; Rodrigues et al. 1995; Matthijs et al. 1996; Velasco et al. 1996; DiDonato et al. 1997). These reports gave optimism that the molecular nature of SMA could be clarified but resulted in confusion as

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