Intelligent Ratio: A New Method for Carrier and Newborn Screening in Spinal Muscular Atrophy

Cavdarli B., Ozturk F. N., Guntekin Ergun S., ERGÜN M. A., DOĞAN Ö., Percin E. F.

GENETIC TESTING AND MOLECULAR BIOMARKERS, vol.24, no.9, pp.569-577, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.1089/gtmb.2020.0085
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.569-577
  • Hacettepe University Affiliated: Yes


Aim:Spinal muscular atrophy (SMA) is an inherited, autosomal recessive neuromuscular disease that causes high morbidity and mortality. The prevalence is 1-2/100,000, while the incidence is 1/6000-1/10,000 among live births. Due to the high carrier frequency (1/40-1/60) of SMA, screening can prevent new cases. The aim of the current study was to present the development of a new, quantitative, real-time, polymerase chain reaction (PCR)-based screening test that uses an intelligent ratio (IR) for analyses, as well as a comparison of the results with the gold standard. Materials and Methods:Included in the study were 100 patients with various risk genotypes for survivor motor neuron 1 (SMN1) andSMN2genes whose genetics had been previously investigated using multiplex ligation probe amplification (MLPA). A combination of the 5 ' nuclease assay and allele-specific PCR was used to quantify the SMN1 deletion mutation with real-time PCR using theFIIgene as a reference. All of the optimized standards were adapted to software that provided automated analyses. The approval number of institutional ethics committee for the study is 2012-KAEK-15/1497. Results:The results of the screening test were completely compatible with the MLPA results; it had achieved 100% sensitivity and specificity compared with the gold standard. The use of the IR in the analyses provided a user-independent method that quickly and accurately provided results, regardless of the amount of DNA used of the extraction method. Conclusion:Carrier or newborn screening of SMA is essential in countries that have high rates of consanguineous marriages. The screening test presented in this study that usesFIIas a reference gene proved to be low-cost, reliable, applicable, accurate, and amenable to use in an automated system for SMA screening.