Association between HBA locus copy number gains and pathogenic HBB gene variants

Avcı, Şahin; Toksoy, Güven; Altunoglu, Umut; KARAKAS, ZEYNEP; Aghayev, Agharza; KARAMAN, VOLKAN; UYGUNER, Zehra Oya; akay, nergis; Kalayci, Tugba

doi:10.14744/ijmb.2021.65477

Association between HBA locus copy number gains and pathogenic HBB gene variants

Güven TOKSOY, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Nergis AKAY, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Pediatrik Hematoloji-Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Agharza AGHAYEV, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Volkan KARAMAN, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Şahin AVCI, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Tuğba KALAYCI, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Umut ALTUNOĞLU, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Zeynep KARAKAŞ, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Zehra Oya UYGUNER (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

International Journal of Medical Biochemistry

14 1

Yıl: 2021 Cilt: 4 Sayı: 2 Sayfa Aralığı: 91 - 96 Metin Dili: İngilizce DOI: 10.14744/ijmb.2021.65477 İndeks Tarihi: 03-02-2022

Association between HBA locus copy number gains and pathogenic HBB gene variants

Öz:

Objectives: Alpha (α) and beta (β) thalassemia are the most prevalent genetic hematological disorders. The co-occur rence of silent β-thalassemia with excess α-globin gene copies is associated with the thalassemia intermedia pheno type. This study was an investigation of the α-globulin gene dosage and sequence variations in thalassemia patients. Methods: Multiplex ligation-dependent probe amplification and Sanger sequencing were used to identify the hemo globin subunit alpha 1 (HBA1) and HBA2 gene alterations in 32 patients. Deletion, duplication, and other findings wereanalyzed in the index cases and family members. Results: Four of the 32 cases (12.5%) were found to have gross duplications. Two cases demonstrated α-globin triplica tion, and 2 had a quadruplicated HBA1/2 genes. Affected family members revealed genotype-phenotype correlation.In 1 patient, it was observed that quadruplicated HBA genes co-occurrence with hemoglobin subunit beta (HBB) mu tation was inherited from his mother. Notably, the mother did not demonstrate any thalassemia phenotype. Furtherinvestigation showed that the mother was carrying a single copy HBA gene deletion in the trans allele that explainedher clinical condition. Conclusion: This study examined the effect of increased copies of the HBA gene in HBB gene pathogenic variant car riers. The results indicated that β-thalassemia mutations with a co-occurrence of increased α-globin gene dosage isnot very rare condition. Patients with clinical findings incompatible with their HBB genotypes should be investigatedfor small and gross α-globin gene variants in order to provide genetic counseling and prenatal diagnosis follow-up, asappropriate.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Toksoy G, akay n, Aghayev A, KARAMAN V, Avcı Ş, Kalayci T, Altunoglu U, KARAKAS Z, UYGUNER Z (2021). Association between HBA locus copy number gains and pathogenic HBB gene variants. , 91 - 96. 10.14744/ijmb.2021.65477
Chicago	Toksoy Güven,akay nergis,Aghayev Agharza,KARAMAN VOLKAN,Avcı Şahin,Kalayci Tugba,Altunoglu Umut,KARAKAS ZEYNEP,UYGUNER Zehra Oya Association between HBA locus copy number gains and pathogenic HBB gene variants. (2021): 91 - 96. 10.14744/ijmb.2021.65477
MLA	Toksoy Güven,akay nergis,Aghayev Agharza,KARAMAN VOLKAN,Avcı Şahin,Kalayci Tugba,Altunoglu Umut,KARAKAS ZEYNEP,UYGUNER Zehra Oya Association between HBA locus copy number gains and pathogenic HBB gene variants. , 2021, ss.91 - 96. 10.14744/ijmb.2021.65477
AMA	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z Association between HBA locus copy number gains and pathogenic HBB gene variants. . 2021; 91 - 96. 10.14744/ijmb.2021.65477
Vancouver	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z Association between HBA locus copy number gains and pathogenic HBB gene variants. . 2021; 91 - 96. 10.14744/ijmb.2021.65477
IEEE	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z "Association between HBA locus copy number gains and pathogenic HBB gene variants." , ss.91 - 96, 2021. 10.14744/ijmb.2021.65477
ISNAD	Toksoy, Güven vd. "Association between HBA locus copy number gains and pathogenic HBB gene variants". (2021), 91-96. https://doi.org/10.14744/ijmb.2021.65477

APA	Toksoy G, akay n, Aghayev A, KARAMAN V, Avcı Ş, Kalayci T, Altunoglu U, KARAKAS Z, UYGUNER Z (2021). Association between HBA locus copy number gains and pathogenic HBB gene variants. International Journal of Medical Biochemistry, 4(2), 91 - 96. 10.14744/ijmb.2021.65477
Chicago	Toksoy Güven,akay nergis,Aghayev Agharza,KARAMAN VOLKAN,Avcı Şahin,Kalayci Tugba,Altunoglu Umut,KARAKAS ZEYNEP,UYGUNER Zehra Oya Association between HBA locus copy number gains and pathogenic HBB gene variants. International Journal of Medical Biochemistry 4, no.2 (2021): 91 - 96. 10.14744/ijmb.2021.65477
MLA	Toksoy Güven,akay nergis,Aghayev Agharza,KARAMAN VOLKAN,Avcı Şahin,Kalayci Tugba,Altunoglu Umut,KARAKAS ZEYNEP,UYGUNER Zehra Oya Association between HBA locus copy number gains and pathogenic HBB gene variants. International Journal of Medical Biochemistry, vol.4, no.2, 2021, ss.91 - 96. 10.14744/ijmb.2021.65477
AMA	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z Association between HBA locus copy number gains and pathogenic HBB gene variants. International Journal of Medical Biochemistry. 2021; 4(2): 91 - 96. 10.14744/ijmb.2021.65477
Vancouver	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z Association between HBA locus copy number gains and pathogenic HBB gene variants. International Journal of Medical Biochemistry. 2021; 4(2): 91 - 96. 10.14744/ijmb.2021.65477
IEEE	Toksoy G,akay n,Aghayev A,KARAMAN V,Avcı Ş,Kalayci T,Altunoglu U,KARAKAS Z,UYGUNER Z "Association between HBA locus copy number gains and pathogenic HBB gene variants." International Journal of Medical Biochemistry, 4, ss.91 - 96, 2021. 10.14744/ijmb.2021.65477
ISNAD	Toksoy, Güven vd. "Association between HBA locus copy number gains and pathogenic HBB gene variants". International Journal of Medical Biochemistry 4/2 (2021), 91-96. https://doi.org/10.14744/ijmb.2021.65477