A Rare Case of Hb H Disease and Systemic Lupus Erythematosus.

Anemia is common in patients with systemic lupus erythematosus (SLE). The association between thalassemia and SLE is rare. In this study, we report the first patient who was found to have a severe hemolytic anemia caused by combination of SLE and Hb H disease. The patient had a more severe presentation in the hematological system. Our case indicates that for a patient who was diagnosed with SLE and developed deterioration in her hematological cell lines, investigation of other possible coexisting causes would be warranted.

Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle.

Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.

Male age is more critical to sperm DNA integrity than routine semen parameters in Chinese infertile males.

This retrospective study evaluated the correlation between the sperm DNA integrity results and infertile male age or sperm motility in 654 infertile men undergoing infertility evaluations from 2013 to 2016. The correlation between the results of sperm DNA integrity and male age was positive, while a negative correlation was detected between sperm DNA integrity and sperm motility in all subjects. According to age (≤30, 30-35 and ≥35), men with normozoospermia or abnormal semen parameters were, respectively, divided into groups 1, 2 and 3, or groups A, B and C. The sperm DNA fragmentation index (DFI) and DFI abnormality rates in groups 3 and C were highest among their respective cohorts. But they were not significantly different between groups within the same age range. Statistically significant differences were found in male age, progressive motility, as well as total motility between patients with normal DFIs and those with abnormal DFIs in group C, but not in group 3. Older (≥35 years) infertile men have increased sperm DNA fragmentation, independent of conventional semen parameters. Male age is more critical to sperm DNA integrity than routine semen parameters.

Phenotypic and Genetic Characterization of Botrytis cinerea Population from Kiwifruit in Sichuan Province, China.

Botrytis cinerea (anamorph of Botryotinia fuckeliana) causes gray mold on numerous plants, including kiwifruit. The primary aim of this study was to investigate the phenotypic and genetic characteristics of the Botrytis cinerea population from kiwifruit in Sichuan Province, China. In all, 176 isolates were collected from kiwifruit orchards from eight geographic regions in Sichuan. All isolates were identified as B. cinerea sensu stricto based on the combined datasets, including morphological criteria, determination of the Bc-hch allele, and phylogenetic analysis of the genes RPB2, G3PDH, and HSP60. Three colony types (i.e., sclerotial, mycelial, and conidial) were observed on potato dextrose agar after 2 weeks, with sclerotial isolates, the predominant category, accounting for 40.91%. No obvious differences in microscopic characteristics were observed among the three types. Three genotypes of transposable elements were identified in the B. cinerea population: boty, flipper, and transposa types. The most prevalent genotype from different geographic populations of B. cinerea was transposa; in contrast, the flipper genotype accounted for only 3.98% of the total population, whereas the vacuma genotype was absent. According to MAT locus amplification, 87 and 89 isolates are MAT1-1 and MAT1-2 type, respectively, and the two mating types were found to be balanced overall in the population. Forty-eight representative isolates were all able to cause gray mold to some extent, and disease severities were significantly different between the cultivars Hongyang and Hort16A (P < 0.01). Disease severity was significantly greater on young leaves than on mature leaves (P < 0.01). No significant relationship was found between pathogenicity and geographical region, colony type, or transposon distribution. The results obtained in the present study suggest a relatively uniform species diversity of Botrytis but rich phenotypic and genetic differentiation within the B. cinerea population on kiwifruit in China. Utilizing resistant cultivars and rain-shelter cultivation instead of fungicides may be an effective approach to delaying pathogen variability.

[Alleles dropout patterns of Y-short tandem repeats in infertile males with Y chromosome microdeletions].

Y chromosomal short tandem repeat (Y-STR) typing is the most commonly used genetic technique in forensic studies. However, there may be a limit to the application of Y-STR in forensic science as Y-STR loci are subject to loss or variation caused by the higher chromosomal structures' spontaneous mutation rate. Located in the long arm of the Y chromosome, azoospermia factor (AZF) have been shown to participate in spermatogenesis and its deletion could cause infertility. However, little is known about the Y-STR dropout pattern in individuals with Y chromosome microdeletions. In this study, 85 infertile males with Y chromosome interstitial deletion were identified and special Y-STR allele dropout patterns were analyzed by employing a Y-STR Commercial Kit and a Y chromosome Deletion Kit. Results demonstrate that AZF a region deletion are related to DYS439-DYS389I-DYS389II alleles dropout, while AZF b region or c region deletions correlate to DYS448 allele dropout. Null DYS385-DYS392-DYS448 alleles were observed in AZF b+c+d region deletion individuals. While null DYS390-Y-GATA-H4-DYS385-DYS392-DYS448 alleles were observed in AZF a+b+c+d large region deletion individuals. Our data suggest that Y chromosome microdeletions may indicate specific Y-STR locus dropout patterns.

Alteration of Scn3a expression is mediated via CpG methylation and MBD2 in mouse hippocampus during postnatal development and seizure condition.

Increased expression of sodium channel SCN3A, an embryonic-expressed gene, has been identified in epileptic tissues, which is believed to contribute to the development of epilepsy. However, the regulatory mechanism of SCN3A expression under epileptic condition is still unknown. Here we showed a high level of Scn3a mRNA expression in mouse embryonic hippocampus with gradually decreasing to a low level during the postnatal development and a methylation of a specific CpG site (-39C) in the Scn3a promoter was increased in hippocampus during postnatal development, corresponding to the downregulation of Scn3a expression. Furthermore, in vitro methylation and -39C>T mutation of the Scn3a promoter decreased the reporter gene expression, suggesting an important role of the -39C site in regulating gene expression. We then demonstrated that the sequence containing -39C was a MBD2-binding motif and the CpG methylation of the promoter region increased the capability of MBD2's binding to the motif. Knockdown of MBD2 in mouse N1E-115 cells led to the -39C methylation and the downregulation of Scn3a transcription by decreasing the Scn3a promoter activity. In the hippocampus of seizure mice, the expressions of Scn3a and Mbd2 were upregulated after 10-day KA treatment. At the same time point, the -39C site was demethylated and the capability of MBD2's binding to the Scn3a promoter motif was decreased. Taken together, these findings suggest that CpG methylation and MBD2 are involved in altering Scn3a expression during postnatal development and seizure condition.

Modeling Dravet syndrome using induced pluripotent stem cells (iPSCs) and directly converted neurons.

Severe myoclonic epilepsy of infancy (SMEI, also known as Dravet syndrome) and genetic epilepsy with febrile seizures plus (mild febrile seizures) can both arise due to mutations of SCN1A, the gene encoding alpha 1 pore-forming subunit of the Nav1.1 voltage-gated sodium channel. Owing to the inaccessibility of patient brain neurons, the precise mechanism of mild febrile seizures and SMEI remains elusive, and there is no effective pharmacotherapy. Induced pluripotent stem cells (iPSCs) and induced neurons (iNs) have been successfully generated from patients and applied for modeling various neuronal diseases. In this study, we established iPSC lines from one SMEI patient and one mild febrile seizures patient, respectively. Functional glutamatergic neurons were subsequently differentiated from these iPSCs. Electrophysiological analysis of patient iPSC-derived glutamatergic neurons revealed a hyperexcitable state of enlarged and persistent sodium channel activation, more intensive evoked action potentials and typical epileptic spontaneous action potentials. In consistent with the severity of the symptoms, the hyperexcitability of the neurons derived from SMEI patient was more serious than that of mild febrile seizures patient. Furthermore, the hyperexcitability of the neurons can be alleviated by treatment with phenytoin, a conventional antiepileptic drug. In parallel, iNs were directly converted from patient fibroblasts which also showed a delayed inactivation of sodium channels. Our results demonstrate that both iPSC-derived neurons and iNs from mild febrile seizures and SMEI patients exhibited a hyperexcitable state. More importantly, patient iPSC-derived neurons can recapitulate the neuronal pathophysiology and respond to drug treatment, indicating that these neurons can be potentially used for screening appropriate drugs for personalized therapies.

Promoting reprogramming by FGF2 reveals that the extracellular matrix is a barrier for reprogramming fibroblasts to pluripotency.

Leukemia inhibitory factor and bone morphogenetic protein signaling pathways play important roles in maintaining the self-renewal of mouse embryonic stem cells (ESCs). In contrast, the supplementation of fibroblast growth factor 2 (FGF2) in culture promotes mouse ESC differentiation. It has been proposed that factors that are adverse for maintaining the self-renewal of ESCs might play detrimental roles in the transcription factor-mediated reprogramming of somatic cells to pluripotency. However, recent evidence has revealed that reprogramming efficiency could be improved by FGF2, while the underlying molecular mechanism remains unknown. In this study, we dissected the roles of FGF2 in promoting mouse fibroblast reprogramming and disclosed the molecular mechanism behind this process. We used both primary induction and secondary inducible reprogramming systems and demonstrated that supplementation with FGF2 in the early phase of induced pluripotent stem cell induction could significantly increase reprogramming efficiency. Moreover, we discovered that many extracellular matrix candidate genes were significantly downregulated in fibroblasts treated with FGF2, and in particular, the synthesis of collagen could be greatly reduced by FGF2 treatment. Subsequently, we demonstrated that collagen is a barrier for reprogramming fibroblast cells to pluripotency, and the decreasing of collagen either by collagenase treatment or downregulation of collagen gene expression could significantly improve the reprogramming efficiency. Our results reveal a novel role of the extracellular matrix in mediating fibroblasts reprogramming.

[Clinical value of MLPA in the prenatal gene diagnosis of Duchenne muscular dystrophy].

OBJECTIVE: To investigate the clinical value of multiplex ligation-dependent probe amplification (MLPA) in the prenatal gene diagnosis of high risk pregnant women from Duchenne muscular dystrophy (DMD) families. METHODS: The 155 high risk pregnant women from DMD families were recruited from 2005 to 2012 in 4 hospitals in Guangzhou, such as Southern Hospital of Southern Medical University and the Third Affiliated Hospital of Guangzhou Medical University. Among all the samples, 7 were chorionic villus samples taken from early-stage pregnancy and 148 were amniotic fluid samples from mid-stage pregnancy. After the maternal contamination was eliminated, the fetal DMD gene screening was carried out by using MLPA. The mutation rates in DMD exons were calculated in all the 155 families. RESULTS: (1) Among the 155 fetuses of the DMD high risk pregnant women, there were 72 male fetuses and 83 female fetuses. In the male fetuses, there were 27 sufferers (38%). In the female fetuses, there were 28 carriers (34%). And there were 100 normal fetuses. (2) Among the 27 DMD sufferers, 22 cases were DMD exon homozygous deletions (14.2%, 22/155) and 5 cases were DMD exon duplications (3.2%, 5/155). Among the 28 carriers, 25 cases were gene heterozygous deletions (16.1%, 25/155) and 3 cases were gene heterozygous duplications (1.9%, 3/155). In the 155 families, the DMD mutations mainly occurred in exons 45-52, and the exon 49 had the highest mutation rates of 22 times. (3) Among the 7 cases of prenatal gene diagnosis using chorionic villus samples, 2 fetuses had the identical DMD genotypes with their mothers and probands. One was a DMD sufferer and the other was a carrier. Termination or continuation of pregnancy was suggested based on the genotype of the fetus. CONCLUSIONS: MLPA provides an accurate method in the prenatal diagnosis of DMD. It could be used to distinguish DMD gene homozygous deletions from heterozygous deletions and duplications. Therefore, it is valuable for DMD prenatal diagnosis in high-risk women. Chorionic villus sampling can be applied to the early prenatal diagnosis for DMD disease.

[Establishment of an internal control for directed differentiation using pluripotent stem cell lines derived from heterozygotic twins].

OBJECTIVE: To reprogram amniotic fluid cells into pluripotent stem cells in order to create an optimal internal control model for directed cell differentiation. METHODS: Human amniotic fluid-derived cells (hAFDCs) from heterozygotic twin fetuses were induced by retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4. In vivo pluripotency, differentiation capacity and karyotype of hAFDCs induced pluripotent stem cells (hAFDCs-iPSCs) were determined. RESULTS: hAFDC-iPSCs derived from heterozygotic twins have maintained self renewal, with expression of high pluripotency marker gene detected at both mRNA and protein levels. The cells have maintained their differentiation capacity both in vitro and vivo, and showed normal karyotypes after long-term culturing in vitro. CONCLUSION: hAFDCs-iPSCs derived from heterozygotic twins have good consistency in terms of genetic background, and can provide a good internal control for directed differentiation of iPSCs, and may be used an ideal source for autologous cell replacement therapy in the later life of the fetus.

[Analysis of de novo copy number variations in a family affected with autism spectrum disorders using high-resolution array-based comparative genomic hybridization].

OBJECTIVE: To analyze de novo copy number variations (CNVs) in a Chinese family affected with autism spectrum disorders (ASD). METHODS: Affymetrix Cytogenetics Whole Genome 2.7M Array assay was performed to identify potential CNVs in four members from the family. RESULTS: A total of 89 de novo CNV regions were identified in the autistic siblings. The CNV regions in total have exceeded 1/1000 of the lengths of chromosomes 5, 11 and 14. In addition, de novo CNV regions were also identified at 3p26.1, 4q22.2, and 5p15.2, which encompassed 10 genes associated with nerve development including GRM7, GRID2 and CTNND2. CONCLUSION: A number of nerve development associated genes were at the de novo CNV sites, which may provide new clues for genetic research of ASD. High-resolution array-comparative genomic hybridization is an effective method for detecting submicroscopic chromosomal imbalances.

[Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy].

OBJECTIVE: To identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD. METHODS: Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA). Biopsied muscle samples were examined with HE staining, immnostaining with anti-dystrophin antibody, and electronic microscopy. RESULTS: MLPA assay suggested that both cases were probably due to non-deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed non-contiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti-dystrophin antibody and negative result with C-terminal anti-dystrophin antibody. CONCLUSION: For patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.

[A case of adefovir dipivoxil induced hypophosphataemic osteomalacia and literature review].

OBJECTIVE: To investigate the clinical features and treatment protocol and prognosis for the hypophosphataemic osteomalacia related to adefovir dipivoxil. METHODS: Analysis was made upon a case of patient with chronic hepatitis B developed hypophosphataemic osteomalacia after administration of adefovir dipivoxil. Literature review was carried out to survey the global prevalence of hypophosphataemic osteomalacia after administration of adefovir dipivoxil among patients with chronic hepatitis B. RESULTS: The clinical symptoms started paralleling to the time taking adefovir dipivoxil, and alleviated after the patient withdrawn adefovir dipivoxil 10 weeks and was given phosphorus. Meanwhile, serum inorganic phosphorus recovered to normal (0.98 mmol/L), which lowest level was 0.77 mmol/L. Systematic review of the literature showed that hyperphosphaturia related to adefovir dipivoxil was dose-dependent, time-dependent and reversible. All reported cases of hypophosphataemic osteomalacia secondary to adefovir dipivoxil (10 mg/d) were from Asian population. CONCLUSIONS: Adefovir dipivoxil induced hypophosphataemic osteomalacia is rarely seen in clinical practice. Those patients with chronic hepatitis B who take adefovir dipivoxil, no matter dosages, should take periodical examinations including blood calcium and serum inorganic phosphorus to monitor whether hypophosphataemic osteomalacia occurs. Other anti-virus drugs could be used when it happens.

[Association of mutation types and distribution characteristics of dystrophin gene with clinical symptoms in Chinese population].

Duchenne muscular dystrophy (DMD) is X-linked disorder caused by mutations in the dystrophin gene. To investigate mutation types and distribution characteristics of dystrophin gene in Chinese DMD patients, we used Multiplex Ligation-Dependent Probe Amplification (MLPA) to analyze the dystrophin gene in 720 DMD patients, their mothers, and 20 normal adult males. Results showed that detection rate was 64.9% (467/720) in all the patients, gene deletion rate was 54.3% (391/720), and gene duplication rate was 10.6% (76/720). The rate of deletion mutant occurred in Exon 45-54 was 71.9% (281/391) in all gene deletion patients; meanwhile, the rate of gene duplication occurred in Exon 1-40 was 82.9% (63/76) in all gene duplication ones. In all the patients with gene deletion and duplication, the rate of DMD and IMD was 90.6% (423/467), and BMD, 9.4% (44/467). This indicates that the main reason of duchenne muscular dystrophy is dystrophin gene deletion mutation, which would occur in any gene unevenly with hot spots of mutation. The location and fragment length of gene deletion and duplication cannot decide the severity of clinical symptoms directly.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases.

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

[Development and genetic polymorphism of abnormal pronuclear zygotes after intracytoplasmic sperm injection].

OBJECTIVE: To compare the development of abnormal pronuclear zygotes after intracytoplasmic sperm injection (ICSI) and analyze their genetic polymorphism. METHODS: Four hundred and ninety three abnormal pronuclear zygotes after ICSI were divided into three groups based on the number of pronuclei: 347 nonpronuclear oocytes, 71 monopronuclear zygotes and 75 multipronuclear zygotes. All of them were cultured in the medium of Vitrolife G5 series(TM). Sixteen short tandem repeats (STR) of seven blastocysts were then analyzed by ABI3100. RESULTS: The cleavage rate of nonpronuclear group (25.4%) was lower than that of the others (P<0.01), the proportion of blocked embryos in nonpronuclear group (48.9%) was significantly higher than that of the others (P<0.05), but the blastocyst rate showed no significant difference in three groups (P>0.05). The genetic polymorphism of the 16 STRs showed that the blastocysts from the nonpronuclear and multipronuclear were diploid, and one of the blastocysts from nonpronuclear oocyte was Y-bearing. CONCLUSION: The zygotes with abnormal pronuclei after ICSI might have development potential, and the blastocysts from nonpronuclear oocytes and multipronuclear zygotes could be diploid.

[Sperm acrosin activity helps predict IVF-ET outcome].

OBJECTIVE: To investigate the effect of sperm acrosin activity on the IVF-ET outcome. METHODS: We analyzed sperm parameters, morphology and acrosin activity for 909 infertile husbands by computer-assisted self-assessment (CASA), modified Papanicolaou staining and N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA), respectively, and detected the rates of fertilization, cleavage, quality embryos, embryo cryopreservation, implantation, clinical pregnancy and abortion. The wives were identified as normal or with mere oviduct problems. RESULTS: The rate of normal sperm morphology and sperm motility, vitality, rapid progressive velocity and concentration were significantly lower in the abnormal acrosin activity group than in the normal one (P < 0.01). Significant positive correlations were observed between acrosin activity and the above-mentioned semen parameters (P < 0.01). There were no significant differences in the number of retrieved eggs, the rates of cleavage, quality embryos, embryo cryopreservation, non-embryo transfer cycles and miscarriages, and the number of transferred embryos between the two groups (P > 0.05). The fertilization rate, the percentage of transfer cycles with only 1 embryo and the rate of implantation and clinical pregnancy were notably higher in the normal acrosin activity group than in the abnormal one (P < 0.01). CONCLUSION: Sperm acrosin activity is closely related with semen parameters, and it helps to predict the sperm fertilizing capacity and IVF-ET outcome.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

[Detection of genomic duplications and deletions of the DMD gene in affected males and female carriers by using mutiplex ligation-dependent probe amplification].

OBJECTIVE: To detect genomic deletion and duplication mutations in the dystrophin gene of the Duchenne muscular dystrophy (DMD) patients and their potential female carriers. METHODS: Genomic deletions and duplications of the DMD gene in 32 affected males and 27 potential female carriers were screened by mutiplex ligation-dependent probe amplification (MLPA). RESULTS: Of the 32 investigated affected males, 24 were detected to have deletions of one or more exons of the DMD gene, 1 patient had a duplication from exon 5 to 55, 1 patient had a nonsense point mutation (R768X) in exon 19, the other 6 affected males were predicted to have possible disease-causing point mutations. MLPA analysis showed a DMD deletion or duplication in 18 female relatives, and the female carriers had the same deletion or duplication as their probands, respectively. CONCLUSION: MLPA analysis is proven to be an efficient tool for identification of both affected males and female carriers of DMD rearrangements in cases in which the disease-causing mutation in the affected male was not known. It could provide useful information for the genetic counseling of the family involved.