Molecular diagnostic yield of exome sequencing in a Chinese cohort of 512 fetuses with anomalies.

Background: Currently, whole exome sequencing has been performed as a helpful complement in the prenatal setting in case of fetal anomalies. However, data on its clinical utility remain limited in practice. Herein, we reported our data of fetal exome sequencing in a cohort of 512 trios to evaluate its diagnostic yield.

Synonymous variant at the terminal nucleotide in exon 3 of F7 causes abnormal splicing: A case report.

Background: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells.

SLC10A5 deficiency causes hypercholanemia.

Background And Aims: Solute Carrier Family 10 Member 5 (SLC10A5) is a member of SLC10, comprising transporters of bile acids, steroidal hormones, and other substrates, but its function remains unclear. The aim of the current investigation was to clarify its function in the metabolism of bile acid and hypercholanemia.

Approach And Results: Whole-exome sequencing and Sanger sequencing were used to identify and confirm the variant in the subjects of hypercholanemia.

Identification of four TTN variants in three families with fetal akinesia deformation sequence.

Background: TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset.

Cytosine-guanine-guanine repeats of FMR1 gene negatively affect ovarian reserve and response in Chinese women.

Research Question: Do cytosine-guanine-guanine (CGG) repeats of the FMR1 gene affect ovarian function, ovarian response and assisted reproductive technology (ART) outcomes in Chinese women?

Design: A retrospective cohort study of 5869 women who underwent 8932 ART cycles at Women's Hospital, School of Medicine, Zhejiang University between January 2018 and June 2021. Basic hormone level, oocyte yield, embryo quality and the rate of live birth were considered as main outcome measures to evaluate the effects of CGG repeats on ovarian function, ovarian response and ART outcomes.

Results: The CGG repeats were negatively related to serum anti-Müllerian hormone (AMH), oestradiol, antral follicle count (AFC) and oocyte yield.

Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies.

Background: Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.

Research Design And Methods: In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022.

Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.

Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing.

Case report: A compound heterozygous mutations in broadens the spectrum of asparagine synthetase deficiency in the prenatal diagnosis.

Asparagine synthetase deficiency (ASNSD) is a rare congenital disorder characterized by severe progressive microcephaly, global developmental delay, spastic quadriplegia, and refractory seizures. ASNSD is caused by variations of the ASNS gene. The present study showed a Chinese family with a fetus suffering microcephaly.

Limb girdle muscular dystrophy 23 caused by compound heterozygous mutations of gene.

Introduction: Mutations of gene are associated with congenital muscular dystrophy (CMD). The -related CMD mainly consists of two diseases, merosin deficient congenital muscular dystrophies type 1A (MDC1A) and limb girdle muscular dystrophy 23 (LGMD23). LGMD23 is characterized by slowly progressive proximal muscle weakness, which primarily affects the lower limbs and results in gait difficulties.

Integrated Bioinformatics Analysis to Screen Hub Gene Signatures for Fetal Growth Restriction.

Background: Fetal growth restriction (FGR) is the impairment of the biological growth potential of the fetus and often leads to adverse pregnancy outcomes. The molecular mechanisms for the development of FGR, however, are still unclear. The purpose of this study is to identify critical genes associated with FGR through an integrated bioinformatics approach and explore the potential pathogenesis of FGR.

Validation and depth evaluation of low-pass genome sequencing in prenatal diagnosis using 387 amniotic fluid samples.

Background: Low-pass genome sequencing (LP GS) is an alternative to chromosomal microarray analysis (CMA). However, validations of LP GS as a prenatal diagnostic test for amniotic fluid are rare. Moreover, sequencing depth of LP GS in prenatal diagnosis has not been evaluated.

Noninvasive Prenatal Screening for Common Fetal Aneuploidies Using Single-Molecule Sequencing.

Amplification biases caused by next-generation sequencing (NGS) for noninvasive prenatal screening (NIPS) may be reduced using single-molecule sequencing (SMS), during which PCR is omitted. Therefore, the performance of SMS-based NIPS was evaluated. We used SMS-based NIPS to screen for common fetal aneuploidies in 477 pregnant women.

Prenatal diagnosis of recurrent moderate skeletal dysplasias in lamin B receptors.

The lamin B receptor () gene is located in chromosome 1q42.12 and encodes the lamin B receptor, an intracellular protein that binds to lamin B. mutations are associated with a broad phenotypic spectrum ranging from non-lethal to lethal skeletal dysplasias.

Novel homozygous silent mutation of gene caused Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare inherited disease characterized by mucocutaneous bleeding due to the abnormalities in quantity or quality of platelet membrane GP IIb (CD41) or GP IIIa (CD61). GP IIb and GP IIIa are encoded by the and genes, respectively. Herein, we described a 7-year-old Chinese boy of the consanguineous couple who was diagnosed with GT based on the typical clinical manifestations, absence of blood clot retraction and the reduced expression of CD41 and CD61 in platelets.

Case Report: Prenatal diagnosis of fetal tetrasomy 9p initially identified by non-invasive prenatal testing.

Tetrasomy 9p is a rare syndrome characterized by fetal growth restriction, Dandy-Walker malformation, cardiac anomalies, and facial abnormalities and is discovered by ultrasound during the prenatal examination. Herein, we report a fetus of tetrasomy 9p without obvious phenotypic manifestations during the first trimester that was identified by non-invasive prenatal testing (NIPT). NIPT revealed that the gain of 9p24.

Case report: Prenatal diagnosis of fetal intracranial hemorrhage due to compound mutations in the gene.

Intracranial hemorrhage is a common complication in preterm infants but occasionally occurs in fetuses. Disruptions of the genes, such as the and genes are common genetic causes identified in fetal intracranial hemorrhage; however, the disruptions of the gene are rarely reported. In the current investigation, fetal intracranial hemorrhage and dilated lateral ventricles were observed in three consecutive siblings in a pedigree.

Case Report: mutation caused intellectual disability in a female with skewed X-chromosome inactivation on the mutant allele.

Skewed XCI plays an important role in the phenotypic heterogeneities of many X-linked disorders, even involving in diseases caused by XCI-escaping genes. -related intellectual disability is more common in females and less common in males, who usually inherit from unaffected heterozygous mothers. As an X inactivation (XCI) escaping gene, the role of skewed XCI in the phenotype of mutant female is unknown.

Case Report: Novel splicing mutations in causing MHC class II deficiency.

Mutations of the Regulatory Factor X5 () have been associated with the autosomal recessive major histocompatibility class II (MHC-II) deficiency, which is a severe immunodeficiency characterized by constitutive and interferon-gamma induced MHC II expression disorder and leads to the absence of cellular and humoral T-cell response to antigen challenge. The compound heterozygous splicing mutations of : c.353 + 6T>G (maternally inherited) and c.

Prenatal diagnosis of trisomy 8 mosaicism, initially identified by cffDNA screening.

Background: So called cell-free fetal DNA (cffDNA) in the maternal plasma, which is derived from placenta, is widely used to screen fetal aneuploidies, including trisomy 21, 18, 13 and sex chromosomes. Here we reported a case of trisomy 8 mosaicism (T8M), which was initially identified via cffDNA screening in noninvasive prenatal testing (NIPT).

Methods: A 35-year-old woman received cffDNA screening at 17th week of gestation.

Case report: Prenatal diagnosis of Kagami-Ogata syndrome in a Chinese family.

The aim of this work was to explore the genetic cause of the proband (Ⅲ2) presenting with polyhydramnios and gastroschisis. Copy number variation sequencing (CNV-seq), methylation-specific multiplex PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were used to characterize the genetic etiology. CNV-seq revealed a deletion of 732.