Targeted gene sequencing and hearing follow-up in 7501 newborns reveals an improved strategy for newborn hearing screening.

Hearing loss is a common congenital condition. Concurrent newborn hearing and limited genetic screening has been implemented in China for the last decade. However, the role of gene sequencing screening has not been evaluated.

DVsc: An Automated Framework for Efficiently Detecting Viral Infection from Single-cell Transcriptomics Data.

Single-cell RNA sequencing (scRNA-seq) has emerged as a valuable tool for studying cellular heterogeneity in various fields, particularly in virological research. By studying the viral and cellular transcriptomes, the dynamics of viral infection can be investigated at a single-cell resolution. However, limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs, and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been developed.

Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine.

Background: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine.

Case Presentation: We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.

Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review.

Background: Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits (FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction.

Behavioural deficits of autism spectrum disorder and associations with different gene clusters: a study with the whole-genome transmission disequilibrium test.

Background: Autism spectrum disorder (ASD) is a diverse neurodevelopmental disease primarily distinguished by limited and stereotyped activities as well as impaired social interaction. Due to the high heritability of ASD, research on the disorder has emphasised on identifying the underlying genetic and epigenetic aetiology. Many ASD loci have been identified by genome-wide association studies (GWASs).

NeuroCNVscore: a tissue-specific framework to prioritise the pathogenicity of CNVs in neurodevelopmental disorders.

Background: Neurodevelopmental disorders (NDDs) are associated with altered development of the brain especially in childhood. Copy number variants (CNVs) play a crucial role in the genetic aetiology of NDDs by disturbing gene expression directly at linear sequence or remotely at three-dimensional genome level in a tissue-specific manner. Despite the substantial increase in NDD studies employing whole-genome sequencing, there is no specific tool for prioritising the pathogenicity of CNVs in the context of NDDs.

Genetic diagnostic yields of 354 Chinese ASD children with rare mutations by a pipeline of genomic tests.

To establish an effective genomic diagnosis pipeline for children with autism spectrum disorder (ASD) for its genetic etiology and intervention. A cohort of 354 autism spectrum disorder patients were obtained from Beijing Children's Hospital, Capital Medical University. Peripheral blood samples of the patients were collected for whole genome sequencing (WGS) and RNA sequencing (RNAseq).

Case report: Clinical features and prognosis of two Infants with rhabdomyosarcoma of the tongue.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, and its most common pathological types include embryonal RMS and alveolar RMS. In contrast, spindle cell RMS (SRMS) is a rare type. Moreover, the tongue is a rare primary site of RMS, and infancy is a rare age at onset.

Newborn Genetic Screening Revealed Increased Levels of Biochemical Indicators in Carriers of Heterozygous Variants.

Conventional newborn screening (NBS) is usually based on biochemical methods to predict the risk of inborn errors of metabolism. Recent studies have applied next-generation sequencing in NBS and revealed much more information, including carrier status. Whether these carriers of variants differ from other individuals was not fully determined.

Identification of a novel variant in N-cadherin associated with dilated cardiomyopathy.

Background: Dilated cardiomyopathy (DCM), which is a major cause of heart failure, is a primary cardiac muscle disease with high morbidity and mortality rates. DCM is a genetically heritable disease and more than 10 gene ontologies have been implicated in DCM. encodes N-cadherin and belongs to a superfamily of transmembrane proteins that mediate cell-cell adhesion in a calcium-dependent manner.

Genotypes and clinical intervention of patients with neurofibromatosis type 1 associated dystrophic scoliosis.

Objective: To analyze the genotypic characteristics of patients with neurofibromatosis type 1 (NF1) associated dystrophic scoliosis and to summarize the outcomes of the surgical treatment of these patients.

Methods: Exome sequencing (ES) combined with multiplex ligation-dependent probe amplification (MLPA) was used for genotypic identification. All patients underwent surgical treatments for spinal deformities, and the outcomes of the surgery was summarized by analyzing the clinical and imaging parameters before and after the surgery.

Molecular identification of T-box transcription factor 6 and prognostic assessment in patients with congenital scoliosis: A single-center study.

Background: Congenital scoliosis (CS) is characterized by vertebral malformations. The precise etiology of CS is not fully defined. A compound inheritance of was identified in 10% of patients with CS in Han Chinese and formed a distinguishable subtype named -associated congenital scoliosis (TACS).

A Novel Homozygous Missense Mutation Results in Familial Multiple Intestinal Atresia and Combined Immunodeficiency.

Rare autosomal-recessive variants in tetratricopeptide repeat domain 7A () gene have been shown to cause intestinal and immune disorders of variable severity. Missense mutations in gene, usually retaining most of the functional motifs, is associated with relative milder clinical presentations. In this study, we reported a patient who was suffering from severe multiple intestinal atresia (MIA) with combined immunodeficiency (CID) that led to the pyloric diaphragm, ileum atresia, colon stenosis, and multiple episodes of sepsis.

Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.

Background: Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis.

Clinical Application of Whole Exome Sequencing for Monogenic Disorders in PICU of China.

Objectives: Whole exome sequencing (WES) has been widely used to detect genetic disorders in critically ill children. Relevant data are lacking in pediatric intensive care units (PICUs) of China. This study aimed to investigate the spectrum of monogenic disorders, the diagnostic yield and clinical utility of WES from a PICU in a large children's hospital of China.

Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China.

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in 8 Women and Children's hospitals nationwide in China retrospectively.

[Identification of variants in TNNI3 gene in two children with restrictive cardiomyopathy].

Objective: To identify the pathogenesis in two patients of restrictive cardiomyopathy (RCM) using high-throughput sequencing.

Methods: Peripheral blood samples from the two patients and their parents were collected and genomic DNAs were extracted to conduct targeted next generation sequencing or whole exome sequencing. Bioinformation analysis was performed to identify the pathogenic variants in genes associated with cardiomyopathy, which were further validated by Sanger sequencing.

Biological implications of genetic variations in autism spectrum disorders from genomics studies.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition characterized by atypical social interaction and communication together with repetitive behaviors and restricted interests. The prevalence of ASD has been increased these years. Compelling evidence has shown that genetic factors contribute largely to the development of ASD.

Exome sequencing as the first-tier test for pediatric respiratory diseases: A single-center study.

The high clinical and genetic heterogeneity makes it difficult to reach a confirmative diagnosis of suspected pediatric respiratory inherited diseases. Many patients with monogenic respiratory disorders could be missed without genetic testing. We performed a single-center study in Beijing Children's Hospital to demonstrate the clinical utility of exome sequencing (ES) as a first-tier test by evaluating the diagnostic yields of ES for inherited diseases with respiratory symptoms.

Whole exome sequencing for non-selective pediatric patients with hyperlipidemia.

Background: Hyperlipidemia is a group of conditions with abnormally elevated levels of any or all lipids or lipoproteins in the blood. It is highly heterogeneous both genetically and clinically, which contributes to diagnostic challenges and results in many patients to be underdiagnosed and undertreated in China. Precise diagnosis and early management are critical to reduce the incidence of potential coronary artery disease and cardiovascular disease.

Whole-exome sequencing reveals two variants in the gene in two Chinese patients with left ventricular non-compaction cardiomyopathy.

Importance: Pathogenic variants in the gene are associated with aggressive dilated cardiomyopathy (DCM). Recently, was found to be associated with left ventricular non-compaction cardiomyopathy (LVNC). Thus far, only five families with LVNC have been reported to carry variants in .

Parallel Tests of Whole Exome Sequencing and Copy Number Variant Sequencing Increase the Diagnosis Yields of Rare Pediatric Disorders.

Both whole exome sequencing and copy number variants sequencing were applied to identify the genetic cause of rare pediatric disorders. In our study, we aimed to investigate the diagnostic yield of parallel tests of trio whole exome sequencing and copy number variants sequencing and its clinical utility. After collecting detailed clinical information, a total of 60 patients were referred to parallel tests of whole exome sequencing and copy number variants sequencing, which used shared initial libraries.