Human Molecular Genetics, Vol 5, 359-365, Copyright © 1996 by Oxford University Press
CH Wang, J Xu, TA Carter, BM Ross, MK Dominski, CA Bellcross, GK Penchaszadeh, TL Munsat and TC Gilliam
Previous reports have established that the telomeric copy of the survival
motor neuron (SMNT) gene and the intact copy of the neuronal apoptosis
inhibitory protein (NAIP) gene are preferentially deleted in patients with
spinal muscular atrophy (SMA). Although deletions or mutations in the SMNT
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 SMNT and
NAIP. To evaluate further the part of SMNT in the development of SMA, we
analyzed 280 asymptomatic SMA family members for the presence or absence of
SMNT exons 7 and 8. We report the following observations: (i) 4% of the
sample harbored a polymorphic variant of SMNT exon 7 that looks like a
homozygous deletion; (ii) approximately 1% of the parents are homozygously
deleted for both exons 7 and 8; (iii) one asymptomatic parent lacking both
copies of SMNT exons 7 and 8 displays a 'subclinical phenotype'
characterized by mild neurogenic pathology; (iv) another asymptomatic
parent lacking both SMNT 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 those conducting prenatal tests with these markers.
ARTICLES
Characterization of survival motor neuron (SMNT) gene deletions in asymptomatic carriers of spinal muscular atrophy
Department of Genetics and Development, College of Physicians and Surgeons at Columbia University, New York, NY 10032, USA.
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