Information For Clinical Genetic Counseling Research Articles

Prevalence and molecular spectrum of α- and β-globin gene mutations in Hainan, China

This study investigated prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in 3049 couples with thalassemia in Hainan Province. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. The most commonly detected mutation for α-thalassemia was- SEA/αα (31.53%), followed by - α4.2/αα (11.15%) and - α3.7/αα (11.02%). The most common mutation for β-thalassemia was CD41/42 (30.27%), followed by - 28 (2.56%). Prevalence was highest in the coastal regions and lowest in the Wenchang, Lingao, and Ding'an regions. We also found that the most common gene mutations in Han people and other minority groups were not homogeneous. Prenatal diagnosis showed 556 normal fetuses, 116 with α-thalassemia hydrops, and 134 with β-thalassemia major. Our findings provide important information for clinical genetic counseling regarding prenatal diagnosis for thalassemia major in Hainan Province.

Invasive molecular prenatal diagnosis of alpha and beta thalassemia among Hakka pregnant women.

This study is a retrospective analysis of the prenatal genetic diagnosis results of fetuses with high risk of major thalassemia to provide information for clinical genetic counseling and to better control the birth of major thalassemia child in Hakka population. Totally, 467 fetuses in at-risk pregnancies were collected from Meizhou people's hospital from January 2014 to December 2017. Genomic DNAs were extracted from peripheral blood of the couples and villus, amniotic fluid or cord blood of the fetuses. DNA-based diagnosis was performed using polymerase chain reaction (PCR) and flow-through hybridization technique. Follow-up visits were done half a year after the fetuses were born. Around 467 fetus at-risk pregnancies were performed prenatal diagnosis. We detected 88 CVS samples, 375 amniocentesis fluid samples and, 4 cord blood samples. The 356 fetuses in α-thalassemia families consisted of 69 (19.38%) with Bart's hydrops syndrome, 20 (5.62%) fetuses with Hb H disease, and 184 (51.68%) fetuses with heterozygote. And the 111 fetuses in β-thalassemia families consisted of 31 (27.93%) thalassemia major, 51 (45.95%) fetuses with heterozygote. There are 13 fetuses with α+β-thalassemia, including 2 cases with severe β-thalassemia. DNA-based testing prenatal diagnosis of thalassemia was found to be highly reliable. Our findings provide key information for clinical genetic counseling of prenatal diagnosis for major thalassemia in Hakka pregnant women. Our work plays an important role in the prevention and control of thalassemia in Hakka population. We will also combine other techniques to further improve our molecular prenatal diagnostic capabilities, including the next-generation sequencing (NGS), Sanger sequencing and MLPA.

Molecular prenatal diagnosis of alpha and beta thalassemia in pregnant Hakka women in southern China.

To date, there has been no systematic study of DNA-based prenatal diagnosis of thalassemia in pregnant Hakka women in southern China. A total of 279 pregnant Hakka women with confirmed cases of thalassemia who had been treated at the Meizhou People's Hospital in China's Guangdong Province from January 2014 to December 2016 were here enrolled. Genomic DNA was extracted from peripheral blood of couples and villus, amniotic fluid, or fetal cord blood. DNA-based diagnosis was performed on the tissues of fetuses whose parents had tested positive for α- and β-globin gene mutations were found using polymerase chain reaction (PCR) and flow-through hybridization technique. Follow-up visits were performed 6months after the fetuses were born. Prenatal diagnosis was performed on 279 fetuses in at-risk pregnancies. Here, 211 α-thalassemia fetuses were confirmed, including 41 (19.43%) that tested positive for Bart's hydrops syndrome and 15 (7.11%) for Hb H disease. There were 103 (48.81%) heterozygotes. β-thalassemia was confirmed in 68 fetuses, including 23 (33.82%) with severe thalassemia and 27 (39.71%) heterozygotes. Another 12 cases were confirmed with α+β-thalassemia, including three cases of severe β-thalassemia. DNA-based testing prenatal diagnosis of thalassemia was found to be highly reliable. Our findings provide key information for clinical genetic counseling of prenatal diagnosis for major thalassemia in pregnant Hakka women in southern China.

Gene Diagnosis and Analysis of Clinical Hematological Phenotype of Thailand Deleted α-Thalassemia 1

To investigate the hematologic characteristics and gene diagnosis of patients with Thailand deleted α-thalassemia 1, so as to provide the information for clinical genetic counseling. The clinical data of 32 patients with Thailand delated α-thalassemia 1 were analyzed retrospectively; the hematologic characteristics and gene diagnosis of Thailand deleted type were investigated by using routine hematologic examination, genetic detection of common thalassemia and Thailand deleted α-thalassemia 1. Among 32 cases, the Thailand deleted α-thalassemia 1 heterozygote was found in 29 cases, the Thailand deleted α-thalassemia 1 and α(3.7) gene deletion double heterozygote were found in 1 case, the Thailand deleted α-thalassemia 1 with β-thalassemia (1 case with codons 41-42 mutation heterozygous, 1 case with CD17 mutation heterozygous) was found in 2 cases by detection. The MCV and MCH levels were decreased in all cases of Thailand deleted thalassemia 1, there were significant differences in RBC, MCV, MCH (P<0.05) between normal control and Thailand deletion α-thalassemia 1 group; there were also significant differences in MCHC (P<0.05) between Southeast asia thalassemia and Thailand deleted α-thalassemia 1 group. There are no significant differences in hematological parameters except MCHC between Southeast asia thalassemia and Thailand deleted α-thalassemia 1 group. moreover the Thailand deleted α-thalassemia 1 in a certain proportion exists in area with high incidence of thalassemia, therefor the clinicians should pay more attention to the screen and diagnosis of Thailand delated α-thalassemia and can exactly diagnose the Thailand delected α-thalassemia 1 on the basis of comprehensive analysis of conventional and Thailand delected α-thalassemia 1 detection results, clinical presentation, hematologic parameters and ultrasonic examination, so as to avoid the birth of child with severe and intermidiate type α-thalassemia caused by Thailand deleted α-thalassemia 1.

Prenatal diagnosis of Thailand deletion of α-thalassemia 1 families

To conduct analysis and prenatal diagnosis on 11 couples carrying Thailand deletion (--(THΑI)) α-thalassemia 1, so as to provide information for clinical genetic counseling on α-thalassemia 1. Altogether 11 Thailand deletion (--(THΑI)) α-thalassemia 1 families were collected from Fujian Maternal and Children Health Hospital from May 2009 to September 2015. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the thalassemia mutations in the couples and fetuses. In one family, Thailand deletion α-thalassemia 1 was detected in both the pregnant woman and her husband. In 10 families, Thailand deletion α-thalassemia 1 was detected in either the pregnant women or the husband, while the spouses had α-thalassemia heterozygote (1 combined with β thalassemia heterozygote). Thailand deletion α-thalassemia 1 family members all had lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). In prenatal diagnosis of the 12 fetuses, 4 fetuses were found with hemoglobin(Hb) Bart's hydrops fetalis syndrome, 5 were with α-thalassemia heterozygote, and 3 were normal. For couples with positive hematological phenotype but normal results in routine genetic examination of α-thalassemia, attention should be paid especially for with a history of having babies of hydrops fetalis syndrome or hemoglobin H disease. It is necessary to consider the possibility of the rare Thailand deletion (--(THΑI)) α-thalassemia 1. Prenatal diagnosis for high-risk families plays an important role.

Analysis of prenatal diagnosis results of 206 thalassemia families

Objective To summarize the geographical distribution,phenotype and genotype data of 206 thalassemia families underwent prenatal diagnosis to provide information for clinical genetic counseling and avoid the birth of severe thalassemia children. Methods Totally,206 thalassemia families were collected from Southern Medical University Nanfang Hospital from January 2008 to December 2009.Genomic DNA was extracted from peripheral blood,villus,amniotic fluid or cord blood from the couples or the fetuses.Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the common α and β-thalassemia mutations.DNA sequencing was used to detect the rare mutations.Follow-up visit were done half a year after the fetuses were born. Results The 206 thalassemia families came from 12 provinces and areas across China,including Heilongjiang province.Mutations detected in α-thalassemia families included --SEA/,-α3.7/,-α4.2/,αCS α/ and αQS α/,which were all included in the testing kit. While there were 4 kinds of β-thalassemia mutations,Gγ+ (A γδβ)0,-28(A→C),CD54-58(-TATGGGCAACCCT) and CD37(G→A),could not be identified with routine testing kit. The 57 α-thalassemia families consisted of 11(19.3％) severe thalassemia,induding 8 Bart's hydrops syndrome and 3 Hb H disease,26(45.6％) heterozygote and 20(35.1％) normal infants,and the 149 β-thalassemia majors families consisted of 28 (18.8％) severe thalassemia,82(55.0％) heterozygote and 39 (26.2％) normal infants.Among the β-thalassemia heterozygotes,there was one 13-trisomy.Follow-up visit found that babies with Bart ' s hydrops syndrome (n =8),Hb H disease (n =3),β-thalassemia majors (n =28) and β thalassemia heterozygote combined with 13-trisomy(n=1) were aborted. Conclusions Thalassemia was found in some north area other than south of China,which should be paid more attention by clinicians.Gap-PCR and PCR-RDB technology are effective measures for thalassemia prenatal diagnosis in identifying major thalassemia fetuses before their birth,thus reduce the birth rate of thalassemia baby.But missed diagnosis might exist during the screening,so it is necessary to perform DNA sequencing on those patients with positive symptoms and negative common genetic diagnostic results.At the same time,prenatal diagnosis of chromosomal disorders should not be neglected for high-risk families. Key words: Thalassemia; Prenatal diagnosis; Sequence analysis,DNA

The mutation spectrum of phenylalanine hydroxylase gene in patients with phenylketonuria in Henan province

To investigate the characteristics of the phenylalanine hydroxylase (PAH) gene mutations in patients with phenylketonuria (PKU) in Henan province, China, in order for providing basic information for clinical genetic counseling and prenatal diagnosis. All the exons and partial flanking introns of the PAH gene were detected by polymerase chain reaction (PCR) and bi-directional sequencing in 34 patients with PKU from Henan province. A total of 23 different disease-causing mutations were identified which corresponded to 92.65% (63/68) of the PAH alleles, including 12 missense mutations, 4 nonsense mutations, 4 splicing junction mutations, and 3 deletion mutations. Among them, A156P and P69_S70delinsP(delCTT) were novel mutations; IVS2+ 5G to C, G332E, IVS10-14C to G and L367 to Wfs were reported in Chinese population for the first time according to the PAH database (www.pahdb.mcgill.ca). Among all the 13 exons, exon 7 harbored the most type of mutations, exon 11 and exon 5 the second. The most common mutations included R243Q (17.65%, 12/68), V399V (11.76%, 8/68), IVS4-1G to A (8.82%, 6/68), R400T(7.35%, 5/68), Y166X(5.88%,4/68) and G247R(5.88%, 4/68). In addition, 9 other gene variations were found in this study. The mutation spectrum and frequency of the PAH gene of patients with phenylketonuria in Henan province were slightly different from those from other parts of China.