Objective To discuss the recent effect of professional instruction on patients with type 2 diabetes mellitus. Methods 200 patients with type 2 diabetes mellitus were divided into the observation group and the control group. The observation group received professional instruction while the control group only got doctors'simple advice about the characteristic, results and attentions of diabetes mellitus. Various in dices were determined before and 3 months after intervention and patients compliance was evaluated 3 months after intervention. Results The indices such as blood glucose,glycosylated hemoglobin, urine trace protein, blood lipid, weight index, blood pressue and waistline were different between the two groups(P＜0.05) after intervention although no difference was seen between them before intervention(P＞0.05).The patients compliance in the observation was better compared with the control group(P＜0.01). Conclusion Application of professional instruction proved to be an effective method to alleviate the symptoms of patients with type 2 diabetes mellitus.

OBJECTIVE: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age. METHODS: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed. RESULTS: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria. CONCLUSION This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
Asians/genetics* ; China ; Exome ; Female ; Humans ; Infant, Newborn ; Metabolic Diseases/genetics* ; Mitochondrial Membrane Transport Proteins/genetics* ; Oxidoreductases/genetics* ; Whole Exome Sequencing

Objective To explore the risk factors for retinopathy in patients with metabolic syndrome.Methods A total of 120 patients with metabolic syndrome admitted to Nanyang Central Hospital from July 2021 to July 2023 were selected as the research subjects,and the patients were categorized into the retinopathy group(n=58)and the non-retinopathy group(n=62)according to the results of fundus examination.The clinical data of patients with metabolic syndrome in both groups were collected and compared.10 mL of blood was collected from the elbow vein of patients in both groups,and the hemoglobin level was measured using a fully automatic blood cell analyzer.The levels of total cholesterol(TC),triacylglycerol(TG),high density lipoprotein-cholesterol(HDL-C),and low density lipoprotein-cholesterol(LDL-C)in the two groups were measured using an automatic biochemical analyzer.The glycosylated hemoglobin(HbA1c)level was determined by high-performance liquid chromatography.The estimated glomerular filtration rate(eGFR)was calculated using the chronic kidney disease epidemiology collaboration equation.Multivariate logistic regression analysis was used to determine the risk factors for retinopathy in patients with metabolic syndrome.Results There were no statistically significant differences in smoking history,drinking history,usage rates of hypoglycemic drugs,lipid-lowering drugs and antihypertensive drugs,systolic blood pressure,cataract,TC,TG,HDL-C,LDL-C,and eGFR between the two groups(P＞0.05).The age,disease duration,insulin usage rate,diastolic blood pressure,HbA1c level,and anemia incidence of patients in the retinopathy group were significantly higher than those in the non-retinopathy group(P＜0.05).Multivariate logistic regression analysis showed that older age,longer disease duration,insulin injection,higher diastolic blood pressure,higher HbA1c level,and lower hemoglobin level were independent risk factors for retinopathy in patients with metabolic syndrome(P＜0.05).Conclusion Old age,long disease duration,insulin injection,high systolic blood pressure,high HbA1c level,and low hemoglobin level are independent risk factors for retinopathy in patients with metabolic syndrome.

Objective To investigate the risk factors and risk prediction model of retinal detachment in patients with myopia.Methods The clinical data of myopic patients treated in our hospital from January 2021 to December 2023 were retrospectively analyzed.A total of 128 patients(128 eyes)with myopic retinal detachment who met the requirements were selected as the retinal detachment group,and 128 myopic patients(128 eyes)without retinal detachment were selected as the control group.The clinical data of patients in the two groups were collected and compared,including age,gender,di-opter,education level,affected side,whether to bear load or not,whether to vibrate or not,whether to have cataract or not,whether to have asthenopia or not,blood pressure,history of diabetes,history of ocular trauma,history of ophthal-mic surgery,and retinal thickness.Risk factors related to retinal detachment in myopia were determined through the multi-variate logistic regression analysis,and based on these factors,the risk prediction model was established.The receiver op-erating characteristic(ROC)curve was used to evaluate the predictive value of the model.Results The age,diopter,systolic blood pressure,cataract incidence,asthenopia incidence,ocular trauma and ophthalmic surgery rates of myopic patients in the retinal detachment group were significantly higher than those in the control group(all P＜0.05).The retinal thickness and choroidal thickness of myopic patients in the retinal detachment group were significantly smaller than those in the control group(both P＜0.05).The risk factors for retinal detachment in myopic patients were older age,higher diopter(absolute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner choroid,and thinner retina(all OR＞1,P＜0.05).The areas under the ROC curve(0.95CI)for predication of retinal de-tachment based on age,ocular disease or discomfort,diopter,choroidal thickness,and retinal thickness alone and their combination were 0.668(0.382-0.936),0.645,0.676(0.407-0.942),0.731(0.503-0.933),0.745(0.499-0.983),and 0.844(0.692-0.983),respectively.The area under the curve(0.844),sensitivity,specificity,and accuracy of the prediction model based on the combination of the five indicators were higher,indicating that this model had a better predic-tion effect.Conclusion The risk factors for retinal detachment in myopic patients are older age,higher diopter(abso-lute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner cho-roid,and thinner retina.The risk prediction model constructed based on these factors has a high evaluation effect.

OBJECTIVETo explore the genetic etiology of three families affected with split-hand/split-foot malformation (SHFM).

METHODSPeripheral venous blood samples from 21 members of pedigree 1, 2 members of pedigree 2, and 2 members of pedigree 3 were collected. PCR-Sanger sequencing, microarray chip, fluorescence in situ hybridization (FISH), real-time PCR, and next-generation sequencing were employed to screen the mutations in the 3 families. The effect of the identified mutations on the finger (toe) abnormality were also explored.

RESULTSMicroarray and real-time PCR analysis has identified a duplication in all patients from pedigrees 1 and 3, which have spanned FKSG40, TLX1, LBX1, BTRC, POLL and FBXW4 (exons 6-9) and LBX1, BTRC, POLL and FBXW4 (exons 6-9) genes, respectively. A missense mutation of the TP63 gene, namely c.692A>G (p.Tyr231Cys), was found in two patients from pedigree 2. FISH analysis of chromosome 10 showed that the rearrangement could fita tandem duplication model. However, next-generation sequencing did not identify the breakpoint.

CONCLUSIONThe genetic etiology for three families affected with SHFM have been identified, which has provideda basis for genetic counseling and guidance for reproduction.

Chromosomes, Human, Pair 10 ; genetics ; Female ; Foot Deformities, Congenital ; genetics ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Male ; Mutation ; genetics ; Pedigree

OBJECTIVETo screen for FOXL2 gene mutations in 6 patients with blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlation.

METHODSPeripheral venous blood samples were collected from the patients for the extraction of genomic DNA. PCR and Sanger sequencing were employed to analyze the coding region and flanking sequences of the FOXL2 gene. Pathogenicity of the identified mutations was verified through literature review and bioinformatic analysis.

RESULTSA heterozygous c.672_701dup30 mutation was found in the probands from the two familial cases, while three heterozygous mutations (two were novel), namely c.462_468del (p.Pro156Argfs*113), c.251T to A (p.Ile84Asn) and c.988_989insG (p.Ala330Glyfs*204) were detected in the three sporadic cases. Literature review and bioinformatic analysis indicated that all these mutations are pathogenic.

CONCLUSIONIdentification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blepharophimosis ; diagnosis ; genetics ; China ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Genetic Association Studies ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Skin Abnormalities ; diagnosis ; genetics ; Urogenital Abnormalities ; diagnosis ; genetics ; Young Adult

OBJECTIVE: To explore the correlation between Fragile X mental retardation gene-1 (FMR1) gene CGG repeats with diminished ovarian reserve (DOR). METHODS: For 214 females diagnosed with DOR, DNA was extracted from peripheral blood samples. FMR1 gene CGG repeats were determined by PCR and capillary electrophoresis. RESULTS: Three DOR patients were found to carry FMR1 premutations, and one patient was found to carry gray zone FMR1 repeats. After genetic counseling, one patient and the sister of another patient, both carrying FMR1 permutations, conceived naturally. Prenatal diagnosis showed that both fetuses have carried FMR1 permutations. CONCLUSION FMR1 gene permutation may be associated with DOR. Determination of FMR1 gene CGG repeats in DOR patients can provide a basis for genetic counseling and guidance for reproduction.
Female ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/genetics* ; Humans ; Ovarian Diseases ; Ovarian Reserve/genetics* ; Primary Ovarian Insufficiency/genetics* ; Trinucleotide Repeats/genetics*

Objective:To explore the genetic etiology for a premature ovarian insufficiency (POI) patient from a consanguineous Chinese family, and to provide basis for genetic counseling and fertility counseling.Methods:Whole-exome sequencing was performed using DNA extracted from the blood sample of POI patient. Suspected pathogenic mutation was analyzed by bioinformatics methods and verified by Sanger sequencing. The pathogenicity of the variation was assessed according to the ACMG genetic variation classification criteria and guidelines.Results:A homozygous variation, c. 32G>T (p.G11V), of PSMC3IP was identified in the patient. Bioinformatics analysis revealed that the variation was conserved in different animal species, and this variation was classified as possible pathogenic variation according to the ACMG genetic variation classification criteria and guidelines.Conclusions:The homozygous missense variation of PSMC3IP is the cause of the POI patient in this family. We are reporting for the first time the missense variation in PSMC3IP gene caused POI, which enriched the mutation spectrum of PSMC3IP and provided the basis for genetic counseling and fertility guidance of this family.

OBJECTIVE: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women. RESULTS: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M. CONCLUSION Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.
China ; Dystrophin/genetics* ; Exons ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD). METHODS: For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos. RESULTS: The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor. CONCLUSION Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.
Male ; Pregnancy ; Child ; Humans ; Female ; Muscular Dystrophy, Duchenne/diagnosis* ; Dystrophin/genetics* ; Mosaicism ; Exons ; Prenatal Diagnosis/methods* ; Nucleotides