Ch. Wang et al., CHARACTERIZATION OF SURVIVAL MOTOR-NEURON (SMN(T)) GENE DELETIONS IN ASYMPTOMATIC CARRIERS OF SPINAL MUSCULAR-ATROPHY, Human molecular genetics, 5(3), 1996, pp. 359-365
Previous reports have established that the telomeric copy of the survi
val motor neuron (SMN(T)) gene and the intact copy of the neuronal apo
ptosis inhibitory protein (NAIP) gene are preferentially deleted in pa
tients with spinal muscular atrophy (SMA), Although deletions or mutat
ions in the SMN(T) gene are most highly correlated with SMA, it is not
clear to what extent NAIP or other genes influence the SMA phenotype,
or whether a small fraction of SMA patients actually have functional
copies of both SMN(T) and NAIP, To evaluate further the part of SMN(T)
in the development of SMA, we analyzed 280 asymptomatic SMA family me
mbers for the presence or absence of SMN(T) exons 7 and 8, We report t
he following observations: (i) 4% of the sample harbored a polymorphic
variant of SMN(T) exon 7 that looks like a homozygous deletion; (ii)
approximately 1% of the parents are homozygously deleted for both exon
s 7 and 8; (iii) one asymptomatic parent lacking both copies of SMN(T)
exons 7 and 8 displays a 'subclinical phenotype' characterized by mil
d neurogenic pathology; (iv) another asymptomatic parent lacking both
SMN(T) exons showed no signs of motor neuron disorder by clinical and
neurodiagnostic analyses, The demonstration of polymorphic variants of
exon 7 that masquerade as homozygous nulls, and the identification of
SMA parents who harbor two disease alleles, serve as a caution to tho
se conducting prenatal tests with these markers.