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CC BY 4.0 · Glob Med Genet 2023; 10(03): 240-246
DOI: 10.1055/s-0043-1774307
Original Article

Lessons from Real Life Experience: Importance of In-House Sequencing and Smart Ratio-Based Real-Time PCR Outperform Multiplex Ligation-Dependent Probe Amplification in Prenatal Diagnosis for Spinal Muscular Atrophy: Bench to Bedside Diagnosis

Gulten Tuncel
1   Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Cyprus
2   DESAM Research Institute, Near East University, Nicosia, Cyprus
,
Burcin Sanlıdag
3   Department of Paediatrics, Faculty of Medicine, Near East University, Nicosia, Cyprus
,
Eray Dirik
3   Department of Paediatrics, Faculty of Medicine, Near East University, Nicosia, Cyprus
,
Tugba Baris
4   Gelişim Tıp Laboratuvarları, Istanbul, Turkey
,
Mahmut Cerkez Ergoren 
1   Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Cyprus
,
Sehime Gulsun Temel
5   Department of Medical Genetics, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
6   Department of Translational Medicine, Institute of Health Science, Bursa Uludag University, Bursa, Turkey
7   Department of Histology and Embryology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
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Abstract

Spinal muscular atrophy (SMA) is a rare, recessively inherited neurodegenerative disorder caused by the presence of pathogenic variants in the SMN gene. As it is the leading inherited cause of infant mortality, identification of SMN gene pathogenic variant carriers is important for diagnostic purposes with effective genetic counseling. Multiple ligation probe analysis (MLPA), a probe-based method, is considered as the gold standard for SMA carrier analysis. However, MLPA might give false-negative results in cases with variations in the probe-binding regions. Here, we present a case born to consanguineous SMA carrier parents. Prenatal diagnosis with MLPA failed to detect the compound heterozygous mutant state of the proband and she was born unfortunately with SMA phenotype. Further analysis with a real-time polymerase chain reaction kit was able to detect the compound heterozygous state of the patient and was confirmed with targeted next-generation sequencing technology.

Keywords

SMA - SMN1 - MLPA - sequencing - in-house testing


Publication History

Article published online:
31 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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