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Published on: May 11, 2018
A More Clinically Effective Long-Read Sequencing-Based Approach for Comprehensive Analysis of Spinal Muscular Atrophy
Shuyuan Li1, Bailing Liu2, Jingfan Zhang3
1International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China; Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
None:
Conventional methods for spinal muscular atrophy (SMA) screening have been challenging in detecting SMN1/2 single-nucleotide variants (SNVs) and small insertions and deletions, SMN1 2 + 0 silent carrier, and the copy number (CN) of SMN2. To address these limitations, a long-read sequencing (LRS)-based approach termed comprehensive analysis of SMA 2 (CASMA2) was developed. CASMA2 was used to perform CN analysis by integrating Poisson distribution with an endogenous reference gene, the first such method developed for LRS platforms. The performance and clinical feasibility of CASMA2 were evaluated by using 414 retrospective peripheral blood samples and 303 prospective dried blood spot samples. CASMA2 displayed 100% accuracy in SMN1/2 CN analysis and identified the SNVs/insertions and deletions in SMN1/2. CASMA2 also showed the capability of screening for the SMN1 2 + 0 silent carrier with family-trio haplotype analysis. It achieved a 99.0% (410 of 414) first-attempt success rate for long-term peripheral blood samples and a 98.7% (299 of 303) rate for dried blood spot samples. CASMA2 offers a clinically feasible, precise, and efficient method for SMA carrier and newborn screening.
