ISSN:
1364-6753
Keywords:
Keywords: 5q SMA, non-deletion patients, quantitative PCR, point mutations
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
ABSTRACT The telomeric survival motor neuron (SMNT gene is a valuable molecular diagnostic tool for childhood-onset spinal muscular atrophy (SMA) as homozygous deletions of SMNT exon 7 (Δ7SMNT) are present in ∼94% of patients. In this report, we provide the first comprehensive study of 32 unrelated non-deletion SMA patients. Quantitative polymerase chain reaction (PCR) studies established that 90% had two intact copies of SMNT exon 7 suggesting that that these patients do not have 5q SMA. Once 5q SMA is confirmed, the SMNT gene can be screened for subtle mutations. Using single strand conformation analysis, we identified two missense mutations (P245L and Y272C) in exon 6 of the SMNT gene of two SMA patients shown to have a single copy of SMNT exon 7. Y272 is most likely critical for SMNT function as it is target for recurring mutations and is associated with type I SMA. These results emphasize the need for dosage analysis in the differential diagnosis of 5q SMA in non-deletion patients, consistent with extensive clinical heterogeneity and some genetic heterogeneity in this disease. Homozygosity or heterozygosity for a Δ7SMNT allele confirms the diagnosis of 5q SMA with greater precision than clinical examination alone.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s100480050021
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