Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States
Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States
复制标题
美国东南部纯合性 β 地中海贫血黑人患者的临床和遗传异质性
DOI：
10.1182/blood.v72.3.1007.1007
复制
发表时间：
1988
期刊：
影响因子：
20.3
通讯作者：
V. Mckie
中科院分区：
文献类型：
--
作者：
J. Gonzalez‐Redondo;T. Stoming;K. Lanclos;Y. Gu;A. Kutlar;F. Kutlar;T. Nakatsuji;B. Deng;I. Han;V. Mckie
研究了19名纯合子β-地中海贫血的黑人患者和许多亲属中存在的导致β-地中海贫血的各种替换和缺失的存在；所有患者都来自佐治亚州、南卡罗来纳州和阿拉巴马州。方法包括基因定位，用Taq聚合酶扩增基因组DNA，通过与合成的寡核苷酸杂交来鉴定已知的核苷酸替换或单核苷酸缺失，克隆和测序β-珠蛋白基因，以及扩增的基因组DNA测序。在所检测的38条染色体中，21条(55%)发生了第29位的A-|-G替换，8条(21%)发生了第88位的C-|-T替换，3条(8%)发生了第24位密码子的替换，同时还发现了下列异常：第6密码子的移码、第IVS-II基因第848位的C--|-A突变(新)、61密码子的A--|-T突变(新)、1.35kb的缺失(包括5‘端)，一个GGamma(AGammadelta Beta)度地中海贫血和一个仍未确定的地中海贫血决定因素。IVS-II基因第848位C--|-A突变发生在受体序列不变的AG二核苷酸附近的第3外显子5‘端。61位密码子的A-|-T突变(AAG--|-Tag)导致终止密码子的产生，从而导致β-度地中海贫血。各种突变发生在不同单倍型的染色体上，但具有特定突变但具有不同单倍型的染色体属于一个特定的框架，这表明交叉是导致这些不同类型的原因。血红蛋白(Hb)F水平普遍较高(55%~75%，其中1例β/β度患者为98.5%)；少数具有特定单倍型和α-地中海贫血-2杂合子的患者Hb-F水平较低。当C--|-T突变发生在珠蛋白基因C-158位C--|-T突变时，Hb-F的GGamma平均为73.8%，+/-8例为64.8%，-/-1例为34.2%。具有β地中海贫血杂合子的亲属的血液学指标以及Hb F、GGamma和Hb A2水平的变化在一定程度上取决于突变或缺失的类型以及带有β地中海贫血决定簇的染色体的单倍型。
The presence of various substitutions and deletions resulting in beta- thalassemia was studied in 19 black patients with homozygous beta- thalassemia and in numerous relatives; all patients were from Georgia, South Carolina, and Alabama. Methodology included gene mapping, amplification of genomic DNA with Taq polymerase, identification of known nucleotide substitutions or a single nucleotide deletion through hybridization with synthetic oligonucleotides, cloning and sequencing of a beta-globin gene, and sequencing of amplified genomic DNA. Of the 38 chromosomes tested, 21 (55%) had the A\---|-G substitution at nt -29, eight (21%) had the C\---|-T substitution at nt -88, three (8%) had the substitution at codon 24, while one each of the following abnormalities were also detected: frameshift at codon 6, a C\---|-A mutation at nt 848 of the beta IVS-II (new), an A\---|-T mutation at codon 61 (new), a deletion of 1.35 kilobases including the 5′ end of beta, a Ggamma(Agammadelta beta) degree-thalassemia, and one thalassemia determinant that remained unidentified. The C\---|-A mutation at nt 848 of IVS-II occurred at a position 3 nucleotides 5′ to the third exon, adjacent to the invariant AG dinucleotide of the acceptor sequence. The A\---|-T mutation in codon 61 (AAG\---|-TAG) resulted in the creation of a stop codon and thus in beta degree-thalassemia. The various mutations occurred on chromosomes with different haplotypes; however, chromosomes with a specific mutation but with different haplotypes belonged to one specific framework, which suggested that crossovers were responsible for these different types. Hemoglobin (Hb) F levels were generally high (55% to 75% with 98.5% in one patient with beta degree/beta degree); a few patients with specific haplotypes and an alpha-thalassemia-2 heterozygosity had a lower Hb F level. The Ggamma in the Hb F was consistently high when the C\---|-T mutation occurred at nt -158 to the Cap site of the Ggamma-globin gene; seven patients with +/+ at this site had an average Ggamma of 73.8%, eight patients with +/- had 64.8%, and one patient with -/- had 34.2%. Variations in hematologic values and in Hb F, Ggamma, and Hb A2 levels of relatives with a beta- thalassemia heterozygosity depended to some extent on the types of mutations or deletions and on the haplotypes of the chromosomes with the beta-thalassemia determinant.
β-地中海贫血是由于β-S-珠蛋白基因中替换的核苷酸缺失所致。
影响因子：
9.8
作者：
KazazianJr,HH;Orkin,SH;Boehm,CD;Sexton,JP;Antonarakis,SE
通讯作者：
Antonarakis,SE