Identification of a novel frameshift mutation of human androgen receptor gene in a patient featuring complete androgen insensitivity syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of human androgen receptor (AR) gene in a patient with complete androgen insensitivity syndrome (CAIS).</p><p><b>METHODS</b>DNA sequences of 8 exons and exon/intron boundaries of the AR gene were amplified with PCR and directly sequenced.</p><p><b>RESULTS</b>DNA sequencing has revealed a frameshift mutation due to deletion of nucleotide C at position 3507 in exon 6, which gave rise to a stop codon resulting premature termination for translation.</p><p><b>CONCLUSION</b>A novel frameshift mutation in exon 6 of AR gene probably underlies the disease in our patient.</p>

A community-based genetic screening of large-scale population and prenatal diagnosis for alpha and beta thalassemia in Zhuhai city of Guangdong province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To describe a community-based model for prevention and control of severe alpha and beta thalassemias in Zhuhai city of Guangdong province.</p><p><b>METHODS</b>Couples for premarital medical examination or regular healthcare examination in pregnancy were enrolled in this prospective screening program, which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling. A conventional heterozygote screening strategy was used to determine alpha and beta thalassemia traits in women and their partners according to the standard procedures of hematological phenotype analysis. Then confirmative diagnosis of alpha and beta thalassemia was performed on those couples suspected at-risk for severe thalassemia by using the PCR-based molecular diagnostic assays. The couples at-risk for severe thalassemia were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus.</p><p><b>RESULTS</b>During the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening, with 71.38% coverage of total population recorded in this city for premarital screening. Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias, with 4312 for alpha thalassemia (4.5%) and 2251 for beta thalassemia (2.3%), respectively. One hundred and forty-eight couples were diagnosed to be at-risk for thalassemias, including 103 for alpha thalassemia and 45 for beta thalassemia, respectively. Successful prenatal diagnosis was made for 142 (98 for alpha thalassemia and 44 for beta thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias. Twenty-three cases of hydrops fetalis, 4 of Hb H diseases and 14 of beta thalassemia were identified. All 41 pregnancies with affected fetuses were voluntarily terminated. Thus, this has led to a marked decrease of severe thalassemia syndrome since the program started.</p><p><b>CONCLUSION</b>We presented the first community-based prospective screening program in China for control of alpha and beta thalassemia in Zhuhai city with a population of 1.29 million through premarital or prenatal screening. This model could be used for control of thalassemias and other hemoglobinopathies in other regions of China and also in other developing countries.</p>

Rapid differential diagnosis of thalassemia trait and iron-deficiency anemia with stepwise regression analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a method for rapid differential diagnosis of thalassemia trait (TT) and iron-deficiency anemia (IDA) using stepwise regression analysis.</p><p><b>METHODS</b>Stepwise regression equation was established for differential diagnosis of TT and IDA according to the red cell index, and the accuracy of the differential diagnosis was evaluated using blind analysis.</p><p><b>RESULTS</b>The accuracy of this equation for differential diagnosis of TT and IDA was 86.82%. The sensitivity, specificity and Youden's index in prediction of TT and IDA were 94.29%, 79.66%, 73.9 and 76.92%, 90.52%, and 67.4%, respectively.</p><p><b>CONCLUSION</b>The stepwise regression equation using the red cell index is concise, rapid, and sensitive in differential diagnosis of TT and IDA, and can be well applicable in clinical practice.</p>

Clinical phenotype genotype correlation in children with hemoglobin H disease in Zhuhai area of China / 中华儿科杂志

<p><b>OBJECTIVE</b>Alpha-thalassemia is one of the most common monogene disorders in the world. Most frequently, it is caused by deletions of alpha-globin gene (-alpha or --), and less commonly resulted from the non-deletional mutation (alpha(T)alpha). Hemoglobin H (HbH) disease is the most severe type among survivors of alpha-thalassemia. The clinical presentation of children with the disease was highly heterogeneous. The aim of this study was to investigate the effect of alpha-globin genotypes in the children with HbH disease on predicting the phenotypic severity and to define the factors involved in the disease progress.</p><p><b>METHODS</b>Forty-three children with the disease in Zhuhai area of Guangdong, China were examined by using established techniques to detect genotypes of alpha-globin and to determine all hematological parameters. All detailed clinical data of the cases were recorded. Then clinical and hematological findings, and the correlation with genotypes were evaluated.</p><p><b>RESULTS</b>Six alpha-thalassemia mutations were detected and interacted to produce 5 HbH disease genotypes. Of these genotypes, -alpha(3.7)/--(SEA)(60%), -alpha(4.2)/--(SEA) (19%) and alpha(CS)alpha/--(SEA) (12%) HbH diseases were prevalent in the area. Compared with -alpha(3.7)/--(SEA) HbH disease, significantly lower red blood cell (RBC) count, hemoglobin (Hb), mean corpuscular hemoglobin (MCHC) and HbA(2) (P < 0.05, 0.01, 0.01 and 0.01, respectively), and significantly higher mean corpuscular hemoglobin volume (MCV) and HbH levels (both P < 0.01), and more severe clinical phenotypes were found in the HbH disease with alpha(T)alpha/--(SEA) genotype. While the differences were much more significant when compared with -alpha(3.7)/--(SEA) then compared with -alpha(4.2)/--(SEA) not only in the hematological parameters, but also in the severity of clinical phenotypes. In addition, HbH levels showed anegatively correlation with the RBC count (r = -0.39, P < 0.01).</p><p><b>CONCLUSION</b>The phenotypes of HbH disease may be mainly related to the underlying genotypes. The children with alpha(T)alpha/--(SEA) genotype presented with more severe hematological and clinical phenotypes followed by the -alpha(4.2)/--(SEA) and then -alpha(3.7)/--(SEA) genotypes. But phenotypic severity was not simply related to the degree of alpha-globin deficiency. HbH levels were found to exacerbate anemia. These data might provide comprehensive and very valuable and basic information for the management of HbH disease, genetic counseling and prenatal diagnosis.</p>