To investigate the expressions of placental growth factor (PLGF) in placenta with hypertensive disorders of pregnancy (HDP), 45 women with HDP and 20 normally pregnant women were studied. Among 45 women with HDP, there were 23 cases of severe preeclampsia and one case of eclampsia. The location and level of PLGF proteins was determined by immunohistochemistry and Western blot. The expression of PLGF mRNA in placenta was assessed by reverse transcriptional-polymerase chain reaction (RT-PCR). The results showed that: (1) The distribution of PLGF in placenta with HDP was similar to normal one, which was mainly in the cytoplasm of villous syncytiotrophoblast and villous stroma; (2) The expression of PLGF protein was significantly decreased in placentas with mild and severe preeclampsia compared to the normal ones (0.3 +/- 0.4 vs 0.6 +/- 0.4, 0.2 +/- 0.5 vs 0.6 +/- 0.4, P < 0.01). There were no differences between the gestational hypertension placenta and normal one (0.5 +/- 0.6 vs 0.6 +/- 0.4, P > 0.05); (3) The transcription levels of the PLGF mRNA in placentas with preeclampsia were significantly lower than in normal groups (3.33 +/- 0.39 vs 4.87 +/- 0.60, 1.97 +/- 0.29 vs 4.87 +/- 0.60, P < 0.01), and no differences were found between the gestational hypertension placenta and normal groups. These findings suggest that the abnormal expression of PLGF in placentas is related to the pathogenesis of HDP.
Placenta/*metabolism ; Pre-Eclampsia/*metabolism ; Pregnancy/*metabolism ; Pregnancy Proteins/*biosynthesis ; Pregnancy Proteins/genetics

OBJECTIVE: To explore the genetic basis for an infant featuring developmental delay, hand deformity and hypertonia of extremities. METHODS: Clinical data and peripheral blood samples of the proband and her parents were collected. Following DNA extraction, potential mutations were screened on an Ion PGM platform using a gene panel. Suspected mutation was verified by PCR and Sanger sequencing. RESULTS: A novel heterozygous nonsense mutation, c.2521C>T(p.R841X), was identified in the NIPBL gene. The mutation may cause premature termination of translation of the adhesion protein loading factor at 841st amino acids. The same mutation was not found in her parents and 931 healthy controls, and was absent from public databases including ExAC and 1000G. Bioinformatic analysis suggested the mutation to be disease causing. CONCLUSION The c.2521C>T (p.R841X) mutation of the NIPBL gene probably underlies the Cornelia De Lange syndrome in the infant. Prenatal diagnosis may be provided to this family upon their subsequent pregnancy.
De Lange Syndrome ; diagnosis ; genetics ; Female ; Heterozygote ; Humans ; Infant ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Proteins ; genetics

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.
Female ; Humans ; Infertility, Male/genetics* ; Male ; Membrane Proteins/genetics* ; Mutation ; Pregnancy ; Sperm Injections, Intracytoplasmic ; Spermatozoa

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Huntington disease and provide prenatal diagnosis for them. METHODS: Peripheral venous blood samples were collected from the probands. PCR and capillary gel electrophoresis were used to determine the number of CAG repeats in their IT15 gene. Pre-symptomatic testing was offered to their children and relatives, and prenatal diagnosis was provided to three pregnant women from the two pedigrees. RESULTS: The two probands, in addition with three asymptomatic members, were found to have a (CAG)n repeat number greater than 40. Upon prenatal diagnosis, the numbers of CAG repeats in two fetuses from pedigree 1 were determined as (16, 19) and (18, 19), both were within the normal range. A fetus from pedigree 2 was found to have a CAG repeat number of (15, 41), which exceeded the normal range. CONCLUSION Genetic testing can facilitate the diagnosis of Huntington disease and avoid further birth of affected children.
Child ; Female ; Genetic Testing ; Humans ; Huntington Disease/genetics* ; Nerve Tissue Proteins/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis

ABCC1 gene is expressed in various tissues and organs of the human body, and can transport substrates including drugs, heavy metals, toxic substances and organic anions. Previous research on ABCC1 gene has mostly focused on tumor multidrug resistance. Recently, ABCC1 has been proposed as a candidate gene for hereditary hearing impairment, which has attracted much attention. ABCC1-associated deafness may be related to its role in biological barriers. This article has summarized recent progress in the study of the role of ABCC1 in the blood-testis barrier, placental barrier, blood-brain barrier, blood-labyrinth barrier, which may provide insight into its biological functions.
Biological Transport ; Deafness/genetics* ; Female ; Humans ; Male ; Multidrug Resistance-Associated Proteins/genetics* ; Placenta ; Pregnancy

OBJECTIVE: To investigate the expression of Calponin-1 and Transgenlin in the uterine smooth muscles during normal labor on-sets, and to evaluate their effect on initiating the normal labor. METHODS: A total of 14 uterine bodies and lower segments of human pregnancy were divided to a non-labor group (NIL) and a labor group(IL). Immunohistochemical technology and Western blot were used to determine the expression of Calponin-1 and Transgelin in the 2 groups. RESULTS: Immunohistochemical detection and Western blot showed that Calponin-1 protein in the uterine smooth muscle tissue of the body and the lower uterine segment of smooth muscle tissues had significant difference (P<0.05). The expression of Transgelin in the uterine body smooth muscle tissue in the IL was higher than that in the NIL(P<0.05). In the lower uterine segments of the smooth muscle, the expression of Transgelin was not significantly different in the 2 groups (P>0.05). CONCLUSION Calponin-1 of the uterine smooth muscle and Transgelin of the uterine body smooth muscle may involve in the regulation of uterine smooth muscle contractility, which is closely related to child birth launch.
Adult ; Calcium-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Labor Onset ; metabolism ; Microfilament Proteins ; genetics ; metabolism ; Muscle Proteins ; genetics ; metabolism ; Myometrium ; metabolism ; Pregnancy ; Uterine Contraction ; metabolism

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with infantile hepatitis syndrome. METHODS: Genes associated with liver diseases subjected to high-throughput sequencing. Candidate variants were validated by Sanger sequencing of the proband and his parents. The pathogenicity of the variants was analyzed through bioinformatic analysis. RESULTS: High-throughput sequencing revealed that the proband has harbored c.182T>C (p.F61S) and c.293C>T (p.P98L) variants of the MPV17 gene, which were verified by Sanger sequencing to be inherited from his parents. The variant c.182T>C (p.F61S) was unreported previously and predicted to be likely pathogenic by bioinformatic analysis. CONCLUSION The proband was caused by the compound heterozygous variations of MPV17 gene including c.182T>C (p.F61S) and c.293C>T (p.P98L). Discovery of the novel variant has enriched the spectrum of pathogenic variants of the MPV17 gene.
China ; DNA, Mitochondrial/genetics* ; Female ; Genetic Testing ; Humans ; Membrane Proteins/genetics* ; Metabolism, Inborn Errors/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Syndrome

OBJECTIVE: To identify the causative variants in 13 Chinese pedigrees affected with oculocutaneous albinism (OCA) so as to provide genetic counseling and prenatal diagnosis to them. METHODS: Thirteen unrelated pedigrees with clinically diagnosed OCA were collected and classified based on the manifestation of skin and eyes. With informed consent obtained from the participants, peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate variants were screened by targeted capture and next generation sequencing, and the results were validated by Sanger sequencing. Prenatal diagnosis was provided to the families upon their subsequent pregnancies. RESULTS: Causative variants were detected in all probands, including 10 with compound heterozygotes or homozygotes for TYR gene variants and 3 with compound heterozygotes for OCA2 gene variants. Among these, two variants [TYR: c.650G>C (p.Arg217Pro) and OCA2: c.516-2A>T] were unreported previously. The pathogenicity of the novel TYR: c.650G>C (p.Arg217Pro) variant was verified through bioinformatic analysis and prediction of three dimensional structure of the protein. Prenatal diagnosis was provided to 6 fetuses with a high risk for OCA. Four fetuses were found to be carriers, one did not carry the variants of the proband, and one was affected with OCA. CONCLUSION Identification of the pathogenic variants in the 13 probands, including 2 novel ones, has expanded the mutational spectrum of OCA and enabled genetic counseling and prenatal diagnosis for the families.
Albinism, Oculocutaneous/genetics* ; China ; Female ; Genetic Testing ; Humans ; Membrane Transport Proteins/genetics* ; Monophenol Monooxygenase/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the clinical phenotype and genetic basis for a fetus suspected for Coffin-Siris syndrome. METHODS: Chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were carried out for the fetus. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound at 23rd gestational week has revealed fetal ventriculomegaly. No abnormality was found by CMA, while WES revealed that the fetus has harbored a de novo heterozygous c.2851G>A (p.G951R) variant of the SMARCA4 gene, which was predicted to be pathogenic. CONCLUSION Genetic testing should be considered for fetuses featuring progressive widening of lateral cerebral ventricles.
Female ; Humans ; Pregnancy ; DNA Helicases/genetics* ; Fetus ; Genetic Testing ; Nuclear Proteins/genetics* ; Phenotype ; Transcription Factors/genetics* ; Exome Sequencing

The aim of this study was to investigate the feasibility of using RASSF1A gene as a universal fetal marker in maternal plasma. Two methods of circulating cell-free fetal DNA (cffDNA) extracted from maternal plasma were compared. The better one was chosen for extraction of cffDNA in the 20 pregnant samples. The SRY gene and the RASSF1A gene treated with methylation-sensitive restriction enzyme were amplificated by RT-PCR and the PCR system was optimized. The results showed that the SRY gene was found in 11 out of the 20 pregnant samples, which was consistent with the postnatal sex. Using the optimized PCR system, the specifically amplified fetal-associated methylated RASSF1A gene was found after treatment with BstUI in 18 of the 20 pregnant samples, while the 2 samples failed in detection. It is concluded that the methylated fetal-specific RASSF1A gene can be used as a universal fetal marker for the presence of cffDNA in maternal plasma without fetal gender restrictions. So, it can be used for noninvasive prenatal diagnosis.
DNA ; isolation & purification ; Female ; Fetus ; Humans ; Pregnancy ; Prenatal Diagnosis ; methods ; Tumor Suppressor Proteins ; blood ; genetics