Two large novel alpha-globin gene cluster deletions causing alpha(0)-thalassemia in two Chinese families

• Published in: Gene 2022-10, Vol.840, p.146767-146767, Article 146767
• Main Authors: Jiwu, Lou, Manna, Sun, Ying, Zhao, Youqing, Fu, Haiyang, Chen, Wanfang, Xu, Yanhui, Liu
• Format: Article
• Language: English
• Subjects: De novo; Deletion; α-major regulatory element; α-thalassemia
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146767

•We have characterized two novel 16p13.3 deletions, with a deletion size of 108 Kb and ∼336 Kb, respectively.•The 108-kb deletion arose de novo, the precise 5′ and 3′ breakpoints were identified comprehensively using of molecular methods.•Except for a haematological phenotype of α0-thalassemia, no developmental and neurological abnormalities were noticed in the deletion carriers. Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation, developmental abnormalities and/or speech delay and facial dysmorphism, which is termed ATR-16 syndrome. Here, we reported two novel 16p13.3 deletions involving the α-globin gene cluster and multispecies conserved sequences (MCSs), causing only a phenotype of α-thalassemia. Samples were collected from members of the two families and were subjected to haematological and comprehensive genetic analysis. The novel 108 Kb deletion in family A extends from the non-protein coding RNA gene (WASIR2) to the NPRL3 gene, removing MCS-R1 to R3. This deletion should arise de novo because it wasn’t detected in both parents. The novel 336 Kb deletion in family B should extend from telomere to ∼ chr16:336000, removing the entire α-globin gene cluster. Carriers of these two deletions presented with microcytosis and hypochromic red cells, in accordance with a phenotype of α0-thalassemia carrier. Our study increases the mutation spectrum of α-thalassemia. MCSs deletion should be considered in clinical practice of thalassemia screening and diagnosis.