Identification of a Novel 9.7 kb Deletion Causing α⁰-Thalassemia in Two Pregnant Women in Southern China

Abstract

The technique of combining multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (CGH) and gap-polymerase chain reaction (gap-PCR) is an effective way to locate unknown breakpoints on the α-globin genes. In the current report, a novel deletion was detected in two pregnant women with moderate hematological phenotypes. Multiplex ligation-dependent probe amplification and array CGH revealed a probable 9.7 kb deletion at 16p13.3. The breakpoints were precisely defined by gap-PCR and direct sequencing. This deletion (NG_000006.1: g.32709_42418del) included HBA1, HBA2 and HBQ, which resulted in an α⁰-thalassemia (α⁰-thal) mutation. There would be a 25.0% chance of conceiving an α-thal intermedia or α-thal major (α-TI or α-TM) fetus if the couples are both carriers. Rare large deletions can cause α-thalassemia (α-thal) and the structure analysis of an unknown deletion is important for clinical diagnosis and further genetic counseling.

KEYWORDS:

• α-globin
• α-thalassemia (α-thal)
• molecular diagnosis
• novel mutation

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by Natural Science Foundation of China [81660034], Natural Science Foundation of Guangxi [2016GXNSFAA380078, 2013GXNSFAA019247], the Health Department of Guangxi Province [S201613, Z2014146, Z2016702 and Z2014605], Guangxi Science and Technology Project [Gui 14124004-1-5, Gui 1598012-21, AD7129016] and Research Fund for Young and Middle-Aged Endocrinologists in Kinsey pediatrics.