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

Cavdarli, Busranur
Ozturk, Fatma Nihal
Guntekin Ergun, Sezen
Dogan, Ozlem
Percin, Emriye Ferda
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.


Novel BRCA2 pathogenic genotype and breast cancer phenotype discordance in monozygotic triplets
Duzkale, Neslihan; EYERCİ, NİLNUR; Oksuzoglu, Berna; Teker, Taner; Kandemir, Olcay (Elsevier BV, 2020-04-01)
BRCA1/2 genes with high-penetrance are tumor suppressor and tumor susceptibility genes that play important roles in the homologous recombination mechanism in DNA repair and increase breast cancer risk. Variants in BRCA1 or BRCA2 are the main causes of familial and early-onset breast cancer. This study investigated pathogenic variant belonging to the BRCA2 gene splice region in monozygotic triplets. A 44-year-old woman was diagnosed with breast cancer when she was 32 years old. Her monozygotic sister had a h...
Identification of Three Novel FBN1 Mutations and Their Phenotypic Relationship of Marfan Syndrome
KAYHAN, GÜLSÜM; ERGÜN, MEHMET ALİ; Ergun, Sezen Guntekin; KULA, SERDAR; PERÇİN, Ferda Emriye (Mary Ann Liebert Inc, 2018-07-26)
Background: Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascular systems, is caused by heterozygous pathogenic variants in FBN1. To date, over 1800 different pathogenic variants have been reported.
Flavin containing monooxygenase 3 genetic polymorphisms Glu158Lys and Glu308Gly and their relation to ischemic stroke
Ozcelik, Aysun Turkanoglu; Demirdogen, Birsen Can; Demirkaya, Seref; Adalı, Orhan (Elsevier BV, 2013-05-25)
Ischemic stroke is a multifactorial disease leading to severe long-term disability and it is the third leading cause of death in developed countries. Although many studies have been reported to elucidate etiological and pathological mechanisms of stroke, the genetic and molecular basis of disease remains poorly understood. Recent studies have shown that reactive oxygen species causing oxidative stress play a pivotal role in the pathogenesis of atherosclerosis that is the main cause of a group of cardiovascu...
OZGUC, M; YILMAZ, E; ERDEM, H; COSKUN, T; OZCELIK, U; Togan, İnci Zehra; GOCMEN, A; AYTER, S; OZALP, I (Wiley, 1994-05-01)
The allele frequency of GATT and Mp6D-9 markers was investigated in 32 cystic fibrosis (CF) families. The GATT6 allele was found to be significantly associated with the DELTAF508 mutation. The Mp6D-9 allele 2/GATT6 haplotype was the major haplotype of the mutant alleles. Further analysis of CF alleles for population-specific mutations is underway so that a more direct approach can be taken, especially for families seeking prenatal diagnosis.
Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2, -2B and SPANX-B, during Mesenchymal-to-Epithelial Transition
Yilmaz-Ozcan, Sinem; Sade, Asli; Kucukkaraduman, Baris; Kaygusuz, Yasemin; Senses, Kerem Mert; Banerjee, Sreeparna; GÜRE, ALİ OSMAY (Public Library of Science (PLoS), 2014-09-17)
Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated duri...
Citation Formats
B. Cavdarli, F. N. Ozturk, S. Guntekin Ergun, M. A. ERGÜN, O. Dogan, and E. F. Percin, “Intelligent Ratio: A New Method for Carrier and Newborn Screening in Spinal Muscular Atrophy,” GENETIC TESTING AND MOLECULAR BIOMARKERS, pp. 569–577, 2020, Accessed: 00, 2020. [Online]. Available: