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BMC Medical Genomics Jan 2024Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios...
BACKGROUND
Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported.
METHODS
In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.
RESULTS
Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.
CONCLUSIONS
Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.
Topics: Humans; Female; Pregnancy; Bartter Syndrome; Introns; Mutation; RNA Splicing; China; Antigens, Neoplasm; Adaptor Proteins, Signal Transducing
PubMed: 38238844
DOI: 10.1186/s12920-024-01797-8 -
Malaysian Family Physician : the... 2023Polyhydramnios is defined as an increase in the amount of amniotic fluid during pregnancy. This article presents the case of a 35-year-old G4P3 lady at 28 weeks of...
Polyhydramnios is defined as an increase in the amount of amniotic fluid during pregnancy. This article presents the case of a 35-year-old G4P3 lady at 28 weeks of gestation with suboptimised gestational diabetes Mellitus (GDM). Routine transabdominal ultrasound showed the presence of polyhydramnios, initially thought to be due to suboptimal glucose control. Further evaluation revealed a congenital diaphragmatic hernia with multiple soft markers. Identifying the underlying causes of polyhydramnios can be challenging in primary care settings, which can be attributed to various factors. Although primary care medical officers may not be required to perform detailed scans, they have a crucial role in identifying gross foetal abnormalities. This study highlights the potential for missed diagnoses in primary care settings and the importance of comprehensive prenatal assessments to ensure early detection and appropriate management of polyhydramnios-related conditions in women with GDM.
PubMed: 38213388
DOI: 10.51866/cr.377 -
Cureus Dec 2023An abnormal rise in the amount of amniotic fluid is a frequent prenatal observation called polyhydramnios, which can indicate a number of underlying problems. Even while...
An abnormal rise in the amount of amniotic fluid is a frequent prenatal observation called polyhydramnios, which can indicate a number of underlying problems. Even while it frequently goes undiagnosed during pregnancy, it may be linked to dangerous fetal illnesses. In three cases of newborns with congenital hypotonia, polyhydramnios was the sole prenatal symptom reported in this study. This fact highlights the significance of understanding the possible connection between genetic abnormalities or neurological problems and polyhydramnios, underscoring the responsibility obstetricians have in educating expectant mothers who are at potential risk for these uncommon but serious illnesses. Whole-genome sequencing (WES), an advanced kind of prenatal testing, is essential for determining genetic reasons and assisting families in making decisions. Working together with specialists in fetal medicine is crucial in guaranteeing the best possible treatment and results for the mother and child.
PubMed: 38205489
DOI: 10.7759/cureus.50331 -
Diagnostics (Basel, Switzerland) Dec 2023The echocardiographic monitoring of a fetus with multiple nuchal cords around the fetal neck is important as it may result in cardiac remodeling and preferential...
The echocardiographic monitoring of a fetus with multiple nuchal cords around the fetal neck is important as it may result in cardiac remodeling and preferential streaming, thus affecting the condition of the fetus. The main aim of our study was to assess whether the collision of the umbilical cord around the fetal neck can lead to discrepancies in the size of the pulmonary artery and the aorta in the three-vessel view and to an increase in the size of the heart, which may result from the compression of the carotid arteries caused by the umbilical cord wrapping around the fetal neck. A total number of 854 patients were included in this study and divided into three groups. Group A (control group) included 716 fetuses (84%) without the umbilical cord around the fetal neck. Group B (study group B) included 102 fetuses (12%) with one coil of the umbilical cord around the fetal neck. Group C (study group C) included 32 fetuses (4%) with two coils of the umbilical cord around the fetal neck. The range of the gestational age of the patients considered for this study was 27-40.2 weeks based on the ultrasound biometry and was not statistically different between the analyzed groups A, B and C ( > 0.05). The Pa/Ao index was calculated by dividing the value of the width of the pulmonary artery (in mm) to the width of the aorta (in mm) measured in the ultrasound three-vessel view. We found that fetuses that the fetuses with one and two coils of the umbilical cord around the neck showed significantly higher values of the width of the pulmonary trunk with the unchanged value of the aorta width. Therefore, we also observed significantly higher values of the ratio of the pulmonary trunk to the aorta for the fetuses wrapped with the umbilical cord around the neck compared with the control group without the umbilical cord around the neck (. Moreover, in the fetuses with one and two coils of the umbilical cord around the fetal neck, an increased amount of amniotic fluid was observed, whereas larger dimensions of CTAR in the fetuses with two coils of the umbilical cord around the neck were present ( < 0.05). The wrapping of the fetus with the umbilical cord around the fetal neck may induce the redistribution of blood flow, leading to fetal heart enlargement and disproportion and may be the cause of polyhydramnios.
PubMed: 38201386
DOI: 10.3390/diagnostics14010077 -
Heliyon Jan 2024mutations have been shown to be associated with myotonia, paramyotonia congenita, and periodic paralyses. More recently, loss-of-function variants in the gene were...
mutations have been shown to be associated with myotonia, paramyotonia congenita, and periodic paralyses. More recently, loss-of-function variants in the gene were also noted to be associated with rarer, autosomal recessive forms of congenital myasthenic syndrome and congenital myopathy. Diagnosis is challenging as the initial clinical presentation and histological features on muscle biopsies are non-specific. We report a Han Chinese patient presented with congenital myopathy with two missense variants. The patient had an antenatal history of reduced fetal movements, polyhydramnios and a very preterm birth. At birth, she was noted to have low Apgar score, respiratory distress syndrome and hypotonia. Delayed motor development was noted in early childhood. Dysmorphic features such as an elongated face, dolichocephaly and high arched palate were present. At 16 years of age, the patient developed progressive muscle weakness and was wheelchair-bound by age 20. Muscle biopsy revealed non-specific changes only. Targeted hereditary myopathy panel testing by next generation sequencing revealed two previously unreported missense variants c.1841A > T p.(Asn614Ile) and c.4420G > A p.(Ala1474Thr) in the gene. The clinical features of -related congenital myopathy and myasthenic syndrome were reviewed. This case exemplifies the utility of next generation sequencing in the diagnosis of undifferentiated muscle disease.
PubMed: 38187266
DOI: 10.1016/j.heliyon.2023.e23663 -
Cureus Dec 2023The deletion of the DIS3L2 gene causes the extremely uncommon congenital overgrowth syndrome, known as Perlman syndrome, which is autosomal recessive. Polyhydramnios,...
The deletion of the DIS3L2 gene causes the extremely uncommon congenital overgrowth syndrome, known as Perlman syndrome, which is autosomal recessive. Polyhydramnios, macrosomia, facial dysmorphism, renal dysplasia, and several congenital abnormalities with Wilms tumor propensity are its defining features. Beckwith-Wiedemann syndrome (BWS), prune belly syndrome (PBS), and Simpson-Golabi-Behmel syndrome (SGBS1) have certain similar clinical characteristics with Perlman syndrome. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. Here, we present a case with the classic clinical features of Perlman syndrome and a DIS3L2 gene deletion that was discovered prenatally.
PubMed: 38161545
DOI: 10.7759/cureus.49777 -
Prenatal Diagnosis Feb 2024A new form of transient antenatal Bartter syndrome (aBS) was recently identified that is associated with the X-linked MAGED2 variant. Case reports demonstrate that this... (Review)
Review
A new form of transient antenatal Bartter syndrome (aBS) was recently identified that is associated with the X-linked MAGED2 variant. Case reports demonstrate that this variant leads to severe polyhydramnios that may result in preterm birth or pregnancy loss. There is limited but promising evidence that amnioreductions may improve fetal outcomes in this rare condition. We report a woman with two affected pregnancies. In the first pregnancy, the patient was diagnosed with mild-to-moderate polyhydramnios in the second trimester that ultimately resulted in preterm labor and delivery at 25 weeks with fetal demise. Whole exome sequencing of the amniotic fluid sample resulted after the pregnancy loss and revealed a c.1337G>A MAGED2 variant that was considered diagnostically. The subsequent pregnancy was confirmed by chorionic villi sampling to also be affected by this variant. The pregnancy was managed with frequent ultrasounds and three amnioreductions that resulted in spontaneous vaginal delivery at 37 weeks and 6 days of a viable newborn with no evidence of overt electrolyte abnormalities suggesting complete resolution. A detailed review of the published cases of MAGED2-related transient aBS is provided. Our review focuses on individuals who received antenatal treatment. A total of 31 unique cases of MAGED2-related transient aBS were compiled. Amnioreduction was performed in 23 cases and in 18 cases no amnioreduction was performed. The average gestational age at delivery was significantly lower in cases without serial amnioreduction (28.7 vs. 30.71 weeks, p = 0.03). Neonatal mortality was seen in 5/18 cases without serial amnioreduction, and no mortality was observed in the cases with serial amnioreduction. In cases of second trimester severe polyhydramnios without identifiable cause, whole exome sequencing should be considered. Intensive ultrasound surveillance and serial amnioreduction is recommended for the management of MAGED2-related transient aBS.
Topics: Pregnancy; Humans; Female; Infant, Newborn; Bartter Syndrome; Polyhydramnios; Premature Birth; Fetal Death; Abortion, Spontaneous; Antigens, Neoplasm; Adaptor Proteins, Signal Transducing
PubMed: 38159268
DOI: 10.1002/pd.6508 -
BMJ Case Reports Dec 2023A woman in her 30s at 29 weeks of gestation was diagnosed with a fetal abdominal cyst and polyhydramnios. As the cyst gradually increased in size, an elective caesarean...
A woman in her 30s at 29 weeks of gestation was diagnosed with a fetal abdominal cyst and polyhydramnios. As the cyst gradually increased in size, an elective caesarean section was performed at 38 weeks of gestation. The neonate experienced respiratory distress due to tense abdominal distension shortly after birth. An emergency laparotomy was performed. The intestinal tract was markedly dilated and contiguous with the cyst. The small bowel distal to the dilated intestine had herniated through the defect. The dilated segment was resected, and an ileostomy was created. The operative and histopathological findings suggested segmental dilatation of the intestine (SDI). SDI is a rare gastrointestinal disorder presenting during the neonatal period. It can cause respiratory failure in newborns by compression owing to its large size. SDI should be considered in the differential diagnosis of relatively large abdominal cysts, and collaboration with paediatric surgeons and neonatologists is necessary for successful outcomes.
Topics: Child; Infant, Newborn; Humans; Pregnancy; Female; Cesarean Section; Dilatation; Intestinal Diseases; Intestines; Cysts
PubMed: 38154863
DOI: 10.1136/bcr-2023-256842 -
Prenatal Diagnosis Jan 2024To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical...
To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical information on the fetus and parents was gathered, and genomic DNAs were extracted from the fetal tissue and family members' peripheral blood samples. Exome sequencing on fetal DNA was performed and following bioinformatics analysis, the suspected pathogenic variants were confirmed through Sanger sequencing. Prenatal ultrasound performed at 29 weeks of gestation revealed hydrops fetalis, decreased fetal movements, multiple joint contractures and polyhydramnios. Intrauterine fetal death was noted in the third trimester. Exome sequencing revealed compound heterozygous variants in the TTN gene: a paternally inherited allele c.101227C>T (p.Arg33743Ter) and a maternally inherited c.104254C>T (p.Gln34752Ter) allele. These variants have not been previously reported and are evaluated to be likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. We report a fetus with hydrops fetalis and arthrogryposis multiplex congenita associated with a compound heterozygote in the TTN gene. Our report broadens the clinical and genetic spectrum associated with the TTN-related conditions.
Topics: Pregnancy; Female; Humans; Hydrops Fetalis; Exons; Arthrogryposis; Pregnancy Trimester, Third; Fetus; Connectin
PubMed: 38148006
DOI: 10.1002/pd.6491 -
European Journal of Obstetrics,... Feb 2024To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios.
OBJECTIVE
To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios.
STUDY DESIGN
This was a retrospective study of singleton pregnancies complicated by isolated polyhydramnios that underwent genetic amniocentesis between 2016 and 2021. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray results, and pregnancy outcomes.
RESULTS
A total of 94 singleton pregnancies were included. Three (3.2%) cases with chromosomal abnormalities were detected, including 2 case of trisomy 21 and 1 of 22q21.1 microdeletion. One case was diagnosed as Prader-Willi syndrome caused by maternal uniparental disomy of chromosome 15. Perinatal death occurred in 1 case with severe polyhydramnios, and was retrospectively diagnosed as Bartter syndrome. Of the 90 infants survived, two were identified to have single gene disorders after birth by whole exome sequencing.
CONCLUSION
We first attempted to determine the value of exome sequencing in pregnancies with isolated polyhydramnios. Our results warrant more studies to evaluate advanced genetic testing technologies used in such pregnancies.
Topics: Humans; Pregnancy; Female; Retrospective Studies; Polyhydramnios; Chromosome Aberrations; Pregnancy Outcome; Amniocentesis
PubMed: 38141485
DOI: 10.1016/j.ejogrb.2023.12.030