Identification of the molecular etiology in rare congenital hemolytic anemias using next‐generation sequencing with exome‐based copy number variant analysis
Makaleler > Tam Makale · 2024
Yazarlar: Esra IŞIK, Yesim Aydinok, Canan Albayrak, Basak Durmus, Zeynep Karakas, Mehmet Fatih Orhan, Nazan Sarper, Sultan Aydın, Sultan Aydın, Selma Unal, Yesim Oymak, Nihal Karadas, Aysen Turedi, Davut Albayrak, Funda Tayfun, Deniz Tugcu, Serap Karaman, Serap Karaman, Mahmut TÖBÜ, Ekrem Unal, Alper Ozcan, Sule Unal, Sule Unal, Tekin Aksu, Aysegul Unuvar, Mustafa Bilici, Mustafa Bilici, Fatih Azik, Yilmaz Ay, Sema Aylan Gelen, Emine Zengin, Esin Albudak, Ibrahim Eker, Taner Karakaya, Muhsin Özgür ÇOĞULU, Ferda Ozkinay, Tahir ATİK
European Journal of Haematology, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2024, cilt 113, ss 82-89
DOI: 10.1111/ejh.14194
Özet
OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.