This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.
Humans ; Female ; Pyelonephritis/complications* ; Pregnancy ; Adult ; Multiple Organ Failure/etiology* ; Shock, Septic/etiology* ; Sepsis/etiology* ; Pregnancy Complications ; Pregnancy Complications, Infectious ; Malnutrition/complications*

OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23⁺⁵ weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Female ; Humans ; Pregnancy ; Pedigree ; Cerebellum/abnormalities* ; Abnormalities, Multiple/diagnosis* ; Eye Abnormalities/diagnosis* ; Kidney Diseases, Cystic/diagnosis* ; Phosphoric Monoester Hydrolases/genetics* ; Retina/abnormalities* ; East Asian People ; Mutation

Pregnancy ; Female ; Humans ; Live Birth ; Calcium ; Oocytes ; Pregnancy, Multiple ; Pregnancy Rate ; Retrospective Studies ; Fertilization in Vitro ; Oocyte Retrieval

OBJECTIVES: To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). METHODS: A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. RESULTS: A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). CONCLUSIONS ART is not associated with the risk of BWDT.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Birth Weight ; Pregnancy Outcome ; Infant, Premature ; Infant, Low Birth Weight ; Pregnancy, Multiple ; Premature Birth/epidemiology* ; Retrospective Studies ; Population Surveillance ; Reproductive Techniques, Assisted/adverse effects* ; Pregnancy Complications

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). METHODS: A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.
Child ; Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Fetal Growth Retardation ; Fetus ; Filamins/genetics* ; Genetic Counseling ; Mutation ; Osteochondrodysplasias

OBJECTIVE: To explore the genetic basis for a fetus with limb abnormality and cardiac malformation. METHODS: Clinical data of a fetus diagnosed at the Shandong Provincial Maternal and Child Health Care Hospital on April 30th, 2021 was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. X-inactivation analysis was carried out for the female members of its family. RESULTS: The fetus was found to have meningoencephalocele, absence of bilateral radii, cleft lip, abnormal great arteries, and single umbilical artery at the gestational age of 11+ weeks. Sequencing revealed that the fetus has harbored a hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene, which was maternally inherited. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). X-inactivation analysis has revealed complete skewed X-inactivation in the pregnant woman and her mother. CONCLUSION The hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene probably underlay the multiple malformations in this fetus.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple ; Cleft Lip ; Fanconi Anemia Complementation Group Proteins ; Fetus ; Gestational Age ; Mothers

OBJECTIVE: To explore the genetic basis for a fetus with multiple malformations. METHODS: Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents. RESULTS: Prenatal ultrasound scan at 21⁺⁵ gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c.607C>T (p.Arg203Trp) variant of the ACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing. CONCLUSION Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c.607C>T (p.Arg203Trp) variant of the PACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.
Female ; Pregnancy ; Humans ; Prenatal Diagnosis ; Ultrasonography, Prenatal ; Syndrome ; Fetus ; Abnormalities, Multiple ; Vesicular Transport Proteins

Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.
Abnormalities, Multiple ; Child ; Child, Preschool ; Craniofacial Abnormalities ; Female ; Growth Disorders/genetics* ; Histone-Lysine N-Methyltransferase ; Humans ; Hypertrichosis/genetics* ; Infant ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein ; Pregnancy ; Syndrome

OBJECTIVE: To analyze the phenotype and genetic variant of a fetus with dysplasia of cerebellar vermis. METHODS: Gestational status and family history of the gravida was taken in combination with the imaging results of the fetus. Following elected abortion, fetal tissue and peripheral blood samples of the couple were collected for the extraction of genome DNA. Whole exome sequencing was carried out to screen potential variant associated with the phenotype of the proband. Specific PCR primers were designed to verify the results by Sanger sequencing. RESULTS: Prenatal ultrasound revealed that the fetal vermis cerebellum was poorly developed, which was similar to the previous pregnancy. Whole exome sequencing revealed that the fetus has carried compound heterozygous variants of the CPLANE1 gene, namely c.7978C>T and c.7169delT, which were respectively inherited from the husband and wife. CONCLUSION The c.7978C>T and c.7169delT compound heterozygous variants of the CPLANE1 gene probably underlay the dysplasia of cerebellar vermis in the fetus, which has provided a basis for genetic counseling and prenatal diagnosis.
Abnormalities, Multiple/genetics* ; Cerebellum/diagnostic imaging* ; Eye Abnormalities/genetics* ; Female ; Fetus ; Humans ; Kidney Diseases, Cystic ; Mutation ; Phenotype ; Pregnancy ; Retina/abnormalities*

OBJECTIVE: To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome. METHODS: Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR). RESULTS: WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping. CONCLUSION The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
Abnormalities, Multiple/genetics* ; Cerebellum/abnormalities* ; Eye Abnormalities ; Female ; Genotype ; Humans ; Kidney Diseases, Cystic ; Mutation ; Pedigree ; Phenotype ; Pregnancy ; Retina/abnormalities*