Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/68530
標題: Determination of SMNI/SMN2 gene dosage by a quantitative genotyping platform combining capillary electrophoresis and MALDI-TOF mass spectrometry
作者: Kao, H.Y.
Su, Y.N.
Liao, H.K.
Liu, M.S.
Chen, Y.J.
關鍵字: spinal muscular-atrophy;single nucleotide polymorphisms;primer-extension;beta-thalassemia;de-novo;smn1;mutations;identification;pcr;oligonucleotides
Project: Clinical Chemistry
期刊/報告no:: Clinical Chemistry, Volume 52, Issue 3, Page(s) 361-369.
摘要: 
Background: Spinal muscular atrophy (SMA) is a common inherited and fatal neuromuscular disease caused by deletions and/or mutations that lead to altered concentrations of proteins encoded by the survival motor neuron genes SMN1 and SMN2. Because of the high incidence (at least 1 in 10 000 live births and a carrier frequency of 1 in 35 to 1 in 50) and severity of the disease, precise quantification of SMN1 and SMN2 gene copy numbers is essential for diagnosis and genetic counseling. Methods: We developed a genotyping platform combining capillary electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify absolute gene dosage. The absolute gene dosage can be determined by a multiplexed competitive PCR protocol followed by capillary electrophoresis analysis. The relative SMN1/SMN2 ratio can be analyzed by PinPoint assay followed by MALDI-TOF MS analysis. Results: The complementary assays were evaluated in confirmed cases including 9 affected patients, 33 carriers, and 478 healthy individuals from the general population. We were able to determine all genotypes with different SMN1/SMN2 gene copy number ratios, which unambiguously diagnosed carrier status and the severity of SMA with 100% specificity. Conclusions: This quantitative genotyping platform is suitable for detection of SMA. The described approach may serve as a general quantitative genotyping method for molecular diagnosis of other inheritable diseases. (C) 2006 American Association for Clinical Chemistry.
URI: http://hdl.handle.net/11455/68530
ISSN: 0009-9147
DOI: 10.1373/clinchem.2005.061192
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