Clinical characteristics and identification of novel variants in three unrelated Chinese families with Vissers-Bodmer Syndrome.

Vissers-Bodmer Syndrome, an autosomal dominant disease, is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, hypotonia and autistic features with a highly variable phenotype. It is caused by variants in the CCR4-NOT transcription complex, subunit 1 gene (). However, the pathophysiologic mechanism of the Vissers-Bodmer Syndrome remains unclear.

Application of a Multiplex Ligation-Dependent Probe Amplification-Based Next-Generation Sequencing Approach for the Detection of Pathogenesis of Duchenne Muscular Dystrophy and Spinal Muscular Atrophy Caused by Copy Number Aberrations.

Both Duchenne muscular dystrophy (DMD; OMIM no. 310200) and spinal muscular atrophy (SMA; OMIM no. 253300/253550/253400/271150) are genetic disorders characterized by progressive muscle degeneration and weakness.

Cytopenia: a report of haplo-cord transplantation in twin brothers caused by a novel germline GATA1 mutation and family survey.

Cytopenia due to the abnormal regulation of GATA1 could manifest as varying degrees of thrombocytopenia and/or anemia and more severely in male children than in female children. Here, we describe the case of pancytopenic and transfusion-dependent twin brothers at our center whose bone marrow puncture revealed low bone marrow hyperplasia. Whole-exome sequencing revealed that the twins had a new germline GATA1 mutation (nm_002049: exon 3:c.

Case report: Osteo-oto-hepato-enteric syndrome caused by UNC45A deficiency.

Recently, UNC45 myosin chaperone A (UNC45A) deficiency was identified as a cause of osteo-oto-hepato-enteric syndrome (O2HE) characterized by congenital diarrhea, neonatal cholestasis, deafness, and bone fragility. To date, only a few O2HE cases have been reported in the literature. Here, we present a child from China diagnosed with O2HE with novel compound heterozygous variants in .

Segawa syndrome caused by gene mutation and its mechanism.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase () gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase () gene is rare, we found that the clinical manifestations of seven children with gene mutations are similar to dopa-responsive dystonia.

Case Report: Eosinophilic gastritis with pyloric stenosis in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked recessive immunodeficiency caused by mutations in the forkhead box protein 3 () gene. IPEX is characterized by the onset of intractable diarrhea, type 1 diabetes mellitus (T1DM), and eczema in the early stages of life. The typical clinic triad for IPEX is not always seen.

Clinical characteristics and genetics of ten Chinese children with PRRT2-associated neurological diseases.

Background: Proline-rich transmembrane protein 2 (PRRT2) plays an important role in the central nervous system and mutations in the gene are implicated in a variety of neurological disorders. This study aimed to summarize the clinical characteristics and gene expression analysis of neurological diseases related to the gene and explore the clinical characteristics, therapeutic effects, and possible pathogenic mechanisms of related diseases.

Methods: We enrolled 10 children with mutation-related neurological diseases who visited the Children's Hospital affiliated with the Shanghai Jiaotong University School of Medicine/Shanghai Children's Hospital between May 2017 and February 2022.

Two novel heterozygous truncating variants in identified in patients with neurodevelopmental disorder and brief literature review.

Pathogenic variants in the nuclear receptor superfamily 4 group A member 2 () cause an autosomal dominant neurodevelopmental disorder with or without seizures. Here, we described two patients presenting with developmental delay, language impairment, and attention-deficit hyperactivity disorder. Trio-based whole exome sequencing revealed two novel heterozygous variants, c.

Induced pluripotent stem cells (SHCDNi006-A cells) isolated from the peripheral blood mononuclear cells of a five-month-old Chinese girl with the heterozygous missense mutation (c.2800 G>A) in the KCNT1 gene.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a kind of epileptic encephalopathy with high genetic heterogeneity. The most common pathogenic gene for EIMFS is potassium sodium-activated channel subfamily T member 1 (KCNT1). Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a five-month-old Chinese girl with heterozygous missense mutation (c.

Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency.

Background: Mitochondrial complex I deficiency (MCID) is the most common biochemical defect identified in childhood with mitochondrial diseases, mainly including Leigh syndrome, encephalopathy, macrocephaly with progressive leukodystrophy, hypertrophic cardiomyopathy and myopathy.

Objective: To identify genetic cause in a patient with early onset autosomal recessive MCID.

Methods: Trio whole-exome sequencing was performed and phenotype-related data analyses were conducted.

Generation of an induced pluripotent stem cell line from an Ohtahara syndrome patient with the hemizygous mutation p.Q503Afs*28 (c.1507_1508del) in the ARX gene.

Aristaless-related homeobox (ARX)-related disorders are recessive X-linked intellectual disability disorders. We encountered a patient with a hemizygous mutation (c.1507_1508del) showing intellectual disability, early-onset epileptic encephalopathy and Ohtahara syndrome.

Allogeneic Hematopoietic Stem Cell Transplantation for PEX1-Related Zellweger Spectrum Disorder: A Case Report and Literature Review.

Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment.

Novel Mutations of the ALMS1 Gene in Patients with Alström Syndrome.

Objective Alström syndrome is an autosomal recessive genetic disease caused by a mutation in the ALMS1 gene. Alström syndrome is clinically characterized by multisystem involvement, including sensorineural deafness, cone-rod dystrophy, nystagmus, obesity, insulin resistance, type 2 diabetes and hypogonadism. The diagnosis is thus challenging for patients without this characteristic set of clinical symptoms.

Case Report: A Novel Compound Heterozygous Mutation in in a Chinese Child With Very Early-Onset Inflammatory Bowel Disease.

Very early-onset inflammatory bowel disease (VEO-IBD) is defined as IBD diagnosed in children younger than 6 years of age. VEO-IBD is often associated with a monogenic etiology or primary immune deficiency. Here, we report the case of a 7-month-old Chinese girl diagnosed with VEO-IBD who had a variant in the interleukin-10 receptor A () gene.

Generation and characterization of an iPSC line (SHCMDLi001-A) from a 12-year-old Chinese Han patient with TRAF7 syndrome and of an iPSC line (SHCMDLi002-A) from a control individual.

Mutations in TRAF7 cause developmental delay and cardiac, facial, digital anomalies. c.1964G > A variant was most recurrent, suggesting its essentiality of pathogenicity.

Novel Truncating and Missense Variants in in Patients With Early-Onset Epilepsy.

Progressive myoclonic epilepsy (PME) is a rare neurodegenerative disease, characterized by myoclonic seizures and tonic clonic seizures, with genetical and phenotypical heterogeneity. The semaphorin 6B () gene has been recently reported a causal gene of PME. Independent studies are warranted to further support these findings.

De novo variants in WDR45 underlie beta-propeller protein-associated neurodegeneration in five independent families.

Background: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare, X-linked dominant neurodegenerative disease mainly characterized by developmental delay, intellectual disability, epilepsy in childhood and dystonia, parkinsonism, dementia in adulthood. BPAN is caused by variants in WD repeat domain 45(WDR45), which is characterized by iron accumulation in the basal ganglia, however, it may be atypical in early brain MRI.

Methods: Whole exome sequencing was performed for five parents-offspring trios and phenotype-driven data analyses were conducted.

Spectrum of Germline Mutations and Clinical Features in Unrelated Chinese Patients With Retinoblastoma.

Retinoblastoma (Rb) is a primary intraocular malignant tumor that occurs primarily in children, and results from loss-of-function mutations in the RB transcriptional corepressor 1 () gene. Genetic testing forms the basis of genetic counseling for affected families, as well as for clinical management of this disease. The aim of this study was to identify germline mutations and correlate the identified mutations with the clinical features of Rb patients.

A de novo MAPRE2 variant in a patient with congenital symmetric circumferential skin creases type 2.

Background: Congenital symmetric circumferential skin creases (CSCSC) was initially described five decades ago. Exome sequencing has recently revealed the genetic etiology of CSCSC. Pathogenic variants in TUBB (OMIM# 191130) and MAPRE2 (OMIM# 605789) have been linked to CSCSC1 (OMIM# 156610) and CSCSC2 (OMIM# 616734), respectively, in an autosomal dominant manner.

[Mutation analysis of two pedigrees with suspected oculocutaneous albinism].

Objective: To analyze the clinical presentation and gene of 2 pedigrees with suspected oculocutaneous albinism(OCA), and provide basis for clinical classification, genetic counseling and prenatal diagnosis.

Methods: Variants were identified using next-generation sequencing(NGS) and confirmed by Sanger sequencing in 2 pedigrees with suspected OCA. The pathogenicity of the variants was analyzed according to the American College of Medical Genetics and Genomics (ACMG) standard.

A multiplex ligation‑dependent probe amplification‑based next‑generation sequencing approach for the detection of copy number variations in the human genome.

The aim of the present study was to describe a multiplex ligation‑dependent probe amplification (MLPA)‑based next‑generation sequencing (NGS) assay that exhibited a significantly higher efficiency in detecting copy number variations (CNVs) and known single‑nucleotide variants, compared with traditional MLPA. MLPA polymerase chain reaction products were used to construct a library with indexed adapters, which was subsequently tested on an NGS platform, and the resulting data were analyzed by a series of analytical software. The reads from each probe reflected genetic variations in the target regions, and fragment differentiation was based on the specific base composition of the sequences, rather than fragment length, which was determined by capillary electrophoresis.