Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

Background and Objectives@#Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and playimportant role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. @*Methods@#and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identifynew cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. @*Conclusions@#Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Cost-effectiveness analysis of different screening modes for thalassemia in Hunan Province / 中华围产医学杂志

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Retrospective and cost-effective analysis of the result of Changsha Municipal Public Welfare Program by Noninvasive Prenatal Testing / 中华医学遗传学杂志

OBJECTIVE@#To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program.@*METHODS@#A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed.@*RESULTS@#NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035.@*CONCLUSION@#NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events / 生物医学与环境科学（英文）

Objective@#To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.@*Methods@#A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.@*Results@#The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.@*Conclusion@#Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing / 中华围产医学杂志

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

A typical Say-Barber-Biesecker/Young-Simpson syndrome caused by heterozygous mutation of KAT6B gene / 中华实用儿科临床杂志

A patient with global developmental delay and facial abnormality treated in Hunan Maternal and Child Health Care Hospital in September 2018 was diagnosed as a typical Say-Barber-Biesecker/Young-Simpson syndrome (SBBYSS)accompanied with comprehensive clinical manifestations and genetic testing was carried out.The patient carries a heterozygous synonymous mutation of KAT6B gene (NM_012330.3)c.3147G>A (p.P1049P), thus leading to the formation of a new cleavage site (receptor) and forming a new truncated protein.In Chinese, this is the second typical SBBYSS that has been identified and the first prenatal genetic diagnosis has been performed.This study has broadened the mutation spectrum of SBBYSS caused by the mutation of KAT6B gene in Chinese population.

Low-intensity extracorporeal shock wave therapy promotes recovery of sciatic nerve injury and the role of mechanical sensitive YAP/TAZ signaling pathway for nerve regeneration / 中华医学杂志(英文版)

BACKGROUND@#Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.@*METHODS@#In this project, we explored LiESWT's role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.@*RESULTS@#LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.@*CONCLUSION@#The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

Xq;Yq translocation in a patient with premature ovarian insufficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with premature ovarian insufficiency.@*METHODS@#Chromosomal G-banding and C-banding, single nucleotide polymorphism array (SNP-array), fluorescence in situ hybridization (FISH) and Y chromosome microdeletion assay were used for the analysis.@*RESULTS@#With the combined techniques, the patient was found to carry a Xq;Yq translocation, with a karyotype of 46,X,der(X)t(X;Y)(q25;q12).ish der(X)(Tel XYp+,Tel XYq+,Yq12+).@*CONCLUSION@#Unbalanced Xq;Yq translocation probably underlay the premature ovarian insufficiency in this patient.

Non-invasive prenatal testing and genetic analysis of a fetus with partial trisomy 21 / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with high risk predicted by non-invasive prenatal testing (NIPT).@*METHODS@#Next-generation sequencing (NGS) was used to analyze free fetal DNA (ffDNA) in the maternal plasma. Chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were used to ascertain copy number variation in the fetus and its parents.@*RESULTS@#SNP-array analysis and chromosomal karyotyping revealed that the fetus had a 15.018 Mb duplication at 4q34.1q35.2 and a 7.678 Mb duplication at 21q11.2q21.1, which were derived from a t(4;21)(q34.1;q21.1) translocation carried by its mother.@*CONCLUSION@#NIPT is capable of detecting submicroscopic chromosomal abnormalities of the fetus. Combined use of genetic techniques, in particular SNP-array, is crucial for the diagnosis of partial trisomy 21q in this case.

Genetic analysis of a pedigree with MECP duplication syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a pedigree with mental retardation and hypotonia by using chromosome microarray analysis (CMA), low coverage massive parallel copy number variation sequencing (CNV-seq) and quantitative PCR (qPCR).@*METHODS@#Genomic DNA was extracted from peripheral blood samples from two male patients and healthy members from the pedigree. CNV-seq was carried out for one patient. Suspected CNV was verified by qPCR. CNV-seq or single nucleotide polymorphism array (SNP array) were carried out for another patient and his family members.@*RESULTS@#Both patients showed severe hypotonia and global development delay, in particular language delay. CNV-seq and SNP array indicated that both patients had carried a Xq28 duplication, with spanned 0.26 Mb and 0.42 Mb, respectively. Both duplications encompassed the MECP2 gene. CNV-seq analysis of their family members confirmed that the mother and one sister had carried similar duplications, while an elder brother was normal.@*CONCLUSION@#CNV-seq and CMA are rapid and effective tools for the diagnosis of MECP2 duplication syndrome in children with mental retardation, hypotonia and recurrent infections.

Comparative study of intracavernous pressure and cavernous pathology after bilateral cavernous nerve crushing and resection in rats / 亚洲男科学杂志(英文版)

This study aimed to compare the effects of bilateral cavernous nerve crushing (BCNC) and bilateral cavernous nerve resection (BCNR) on intracavernous pressure (ICP) and cavernous pathology in rats and to explore the optimal treatment time for the BCNC and BCNR models. Seventy-two male rats aged 12 weeks were randomly divided into three equal groups: Sham (both cavernous nerves exposed only), BCNC (BCN crushed for 2 min), and BCNR (5 mm of BCN resected). Erectile function was then measured at 1 week, 3 weeks, and 5 weeks after nerve injury, and penile tissues were harvested for histological and molecular analyses by immunohistochemistry, immunofluorescence, Western blot, and cytokine array. We found that erectile function parameters including the maximum, area, and slope of ICP/mean arterial pressure (MAP) significantly decreased after BCNR and BCNC at 1 week and 3 weeks. At 5 weeks, no significant differences were observed in ICP/MAP between the BCNC and Sham groups, whereas the ICP/MAP of the BCNR group remained significantly lower than that of the Sham group. After BCNC and BCNR, the amount of neuronal-nitric oxide synthase-positive fibers, smooth muscle cells, and endothelial cells decreased, whereas the amount of collagen III content increased. These pathological changes recovered over time, especially in the BCNC group. Our findings demonstrate that BCNC leads to acute and reversible erectile dysfunction, thus treatment time should be restricted to the first 3 weeks post-BCNC. In contrast, the self-healing ability of the BCNR model is poor, making it more suitable for long-term treatment research.

Genetic etiology analysis of 420 children with neurodevelopmental disorders / 中华实用儿科临床杂志

Objective@#To investigate the genetic etiology of neurodevelopmental disorders (NDD), and to provide a theoretical basis for its genetic counseling, family risk evaluation and prenatal diagnosis.@*Methods@#Karyotype analysis and chromosome microarray analysis (CMA) were conducted of the data from 420 children diagnosed accor-ding to NDD diagnostic criteria at Maternal and Child Health Hospital of Hunan Province from January 2016 to December 2018.@*Results@#Among the 420 cases, 14 cases (3.33%, 14/420 cases) with global developmental disabilities/intellectual disabilities (GDD/ID) had chromosomal abnormalities.The location of chromosome breakpoints and the range of deleted or duplicated fragments in 13 cases were further determined by using CMA.In this study, pathogenic copy number variations (CNVs) were detected in 61 children (14.52%, 61/420 cases), which included 31 cases (50.82%, 31/61 cases) of known syndromes, including Angelman/Prader-Will syndrome (8 cases), Williams syndrome (3 cases), Phelan-McDermid syndrome (3 cases) and other 13 syndromes, and 30 cases with clinically significant pathogenic CNVs.Additionally, by the combination of CMA and fluorescence in situ hybridization (FISH), a family were diagnosed with mental retardation caused by 10q26 and 12p13 occult rearrangement.@*Conclusions@#Chromosomal abnormalities and genomic microdeletion/duplication are the primary genetic causes for children with NDD.Combination of karyotype analysis, CMA and FISH can provide definite etiological diagnosis for these children, which has important clinical signi-ficance for the treatment of children and guidance of their parents′ reproduction.

Tandem mass spectrometry screening of 565 182 newborns for inherited metabolic diseases in Hunan province / 中华实用儿科临床杂志

Objective@#To investigate the prevalence, mutation characteristics and clinical outcomes of inherited metabolic diseases(IMD) by using tandem mass spectrometry screening.@*Methods@#In Hunan province, 565 182 newborns who underwent tandem mass spectrometry (MS/MS) screening for IMDs were studied, including fatty acid oxidation disorders (FAODs), amino acid disorders (AAs), and organic acidemias (OAs) between March 2013 and September 2017.For the patients with positive results, a recall screening test was performed, and the results were further confirmed by specific biochemical and genetic analysis.For all the patients with IMD, guideline-directed medical treatment was administrated, and the follow-up outcomes was evaluated.@*Results@#A total of 107 newborns were diagnosed with IMDs, with an overall prevalence of 1∶5 282, including 65 newborns with FAODs (1∶ 8 695), 29 newborns with AAs (1∶19 489), and 13 newborns with OAs (1∶43 476). The primary carnitine deficiency(PCD)(44 cases), hyperphenylalaninemia (HPA)(17 cases), short-chain acyl-CoA dehydrogenase deficiency(SCADD)(12 cases), citrine deficiency(NICCD)(6 cases) were the 4 most common IMDs in Hunan province.The hotspot mutations in SLC22A5 gene of PCD were c. 51C>G(25.3%), c.1400C>G(23.0%), and c. 760C>T(13.8%); in PAH gene of HPA were c. 728G>A (22.2%) and c. 721C>T(14.8%); in ACADS gene of SCADD was c. 1031A>G(38.9%); and in SLC25A13 gene of NICCD was c. 851_854delGTAT (50.0%), respectively.The remaining IMDs were rare, and the hotspot mutations were unclear right now.During a mean follow-up of (26.1±5.6) months, 7 patients died, 4 patients suffered an intelligent disability, whereas the remaining 96 subjects had normal physical and intelligent development.@*Conclusions@#The overall prevalence of IMDs is not fairly low in Hunan province.Newborn screening and early appropriate management can significantly improve the outcomes of these patients.

Genetic analysis of a child with mental retardation and hypospadia / 中华医学遗传学杂志

Objective@#To carry out genetic testing for a boy presenting with mental retardation and hypoplasia.@*Methods@#Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents.@*Results@#SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46, XX, ish ins(11; 2)(p15; q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46, XY, ish der(11)ins(11; 2)(p15; q33q36)mat.@*Conclusion@#SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.

Analysis on the Genotype of 5018 Cases of Thalassemia in Hunan Area / 中国实验血液学杂志

OBJECTIVE@#To investigate the type and distritution of thalassemia gene mutaitons in Hunan area, so as to provide evidence for prenatal screening, diagnosis and reduction of birth defects.@*METHODS@#A total of 5018 cases from Maternal and Children Health Hospital of Hunan from June 2017 to Dec 2018 were undergone thalassemia gene mutation analysis. The reverse dot blot hydridization was used to detect 6 kinds of genotypes of α-thalassemia and 17 kinds of point mutations of β-thalassemia, and the detected data were analyzed statistically.@*RESULTS@#889 cases (55.9%) of α-thalassemia carriers were found, including 385 cases of silent α-thalassemia, 488 cases of α-thalassemia trait, 16 cases of Hb H disease. --/αα was the most common genotype in α thalassemia. 664 cases (41.7%) were diagnosed as β-thalassemia carriers, heterozygotes accounted for 99.8% (663/664), IVS-Ⅱ-654, CD41-42M and CD17M were the main genotypes, and compound heterozygote accounted for 0.2% (1/664). 38 cases were diagnosed as α-thalassemia combined β-thalassemia.@*CONCLUSION@#The constituent ratio of thalassemia gene mutations in Hunan has regional characteristics, --/αα is the most common genotype in α-thalassemia carrier. IVS-Ⅱ-654, CD41-42 and CD17 are common ones in β-thalassemia. The frequency of α-thalassemia combined with β-thalassemia is high.

Genetic analysis of a child with mental retardation and hypospadia / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a boy presenting with mental retardation and hypoplasia.@*METHODS@#Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents.@*RESULTS@#SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46,XX,ish ins(11;2) (p15;q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46,XY,ish der(11)ins(11;2) (p15;q33q36)mat.@*CONCLUSION@#SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.

Prenatal diagnosis of monochorionic-diamniotic twins discordant for 45,X/46,XX mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism.@*METHODS@#Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid.@*RESULTS@#Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis.@*CONCLUSION@#To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.

Identification of a de novo interstitial 21q22.12q22.13 deletion in a patient with intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy.@*METHODS@#Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed.@*RESULTS@#The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo.@*CONCLUSION@#A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.

Tandem mass spectrometry screening of 565 182 newborns for inherited metabolic diseases in Hunan province / 中华实用儿科临床杂志

Objective To investigate the prevalence,mutation characteristics and clinical outcomes of inherited metabolic diseases(IMD) by using tandem mass spectrometry screening.Methods In Hunan province,565 182 newborns who underwent tandem mass spectrometry (MS/MS) screening for IMDs were studied,including fatty acid oxidation disorders (FAODs),amino acid disorders (AAs),and organic acidemias (OAs) between March 2013 and September 2017.For the patients with positive results,a recall screening test was performed,and the results were further confirmed by specific biochemical and genetic analysis.For all the patients with IMD,guideline-directed medical treatment was administrated,and the follow-up outcomes was evaluated.Results A total of 107 newborns were diagnosed with IMDs,with an overall prevalence of 1 ∶ 5 282,including 65 newborns with FAODs (1 ∶ 8 695),29 newborns with AAs (1 ∶ 19 489),and 13 newborns with OAs (1 ∶ 43 476).The primary carnitine deficiency(PCD) (44 cases),hyperphenylalaninemia (HPA) (17 cases),short-chain acyl-CoA dehydrogenase deficiency (SCADD) (12 cases),citrine deficiency(NICCD)(6 cases) were the 4 most common IMDs in Hunan province.The hotspot mutations in SLC22A5 gene of PCD were c.51C ＞ G(25.3％),c.1400C ＞ G(23.0％),and c.760C ＞ T(13.8％);in PAH gene of HPA were c.728G ＞ A (22.2％) and c.721C ＞ T(14.8％);in ACADS gene of SCADD was c.1031A ＞ G(38.9％);and in SLC25A13 gene of NICCD was c.851_854delGTAT (50.0％),respectively.The remaining IMDs were rare,and the hotspot mutations were unclear right now.During a mean follow-up of (26.1 ± 5.6) months,7 patients died,4 patients suffered an intelligent disability,whereas the remaining 96 subjects had normal physical and intelligent devdopment.Conclusions The overall prevalence of IMDs is not fairly low in Hunan province.Newborn screening and early appropriate management can significantly improve the outcomes of these patients.