title: Two novel copy number variations involving the α-globin gene cluster on chromosome 16 cause thalassemia in two Chinese families.
abstract: Copy number variations (CNVs) can cause many genetic disorders and the structure analysis of unknown CNVs is important for clinical diagnosis. The human α-globin gene cluster lies close to the telomere of the short arm on chromosome 16. Copy number variations of this region produce excessive or insufficient α-globin chains which imbalances the β-globin chains, resulting in thalassemia. However, these CNVs usually cannot be precisely defined by traditional methods. Here, we designed a technique strategy and applied it to identify two CNVs involving the α-globin gene cluster causing thalassemia in two Chinese families. A novel 282 kb duplication (αααα(282)) was identified in family A and a novel 235 kb deletion (--(235)) in family B. Proband A is a coinheritance of β(CD41-42) and αααα(282) and showed severe β-thalassemia intermedia phenotype. Proband B is a compound heterozygote of --(235)/α(CS)α genotype and was diagnosed with hemoglobin H disease. The clinical phenotypic features of the CNVs carriers were described, together with a complete picture of molecular structure of these rearrangements. Two CNVs are novel rearrangements in α-globin clusters and the αααα(282) is the first to identify the exact insert position of a duplication region from the telomere on chromosome 16. In a conclusion, successful identification and characterization of these two novel CNVs not only demonstrates the precision and effectiveness of our strategy in analyzing the structure of unknown CNVs, but also extended the spectrum of thalassemia and provide new examples for studying genomic recombination.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.|Guangdong Genetic Testing Engineering Research Center, Guangzhou, 510515, Guangdong, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Shang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yi
authors.affiliation: Liuzhou Key Laboratory of Birth Defects Prevention and Control, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, 545001, Guangxi, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Cai
authors.affiliation: Liuzhou Key Laboratory of Birth Defects Prevention and Control, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, 545001, Guangxi, China.|Department of Clinical Laboratory, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, 545001, Guangxi, China.
authors.forename: Zhetao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Cuixian
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Decheng
authors.initials: D
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. xixm@smu.edu.cn.|Guangdong Genetic Testing Engineering Research Center, Guangzhou, 510515, Guangdong, China. xixm@smu.edu.cn.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D005810:Multigene Family; D010375:Pedigree; D013789:Thalassemia / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics*
chemical_list: D055542:alpha-Globins
keywords: Chinese family; Copy number variation; Thalassemia; α-Globin genes cluster