A Novel m.1636A > G Variant in Mitochondrial TV Gene Might Cause New Phenotype of Mitochondrial Disease in a 2-Year Old Chinese Boy.

Pathogenic variants of mitochondrial DNA (mtDNA) are associated with a large number of heterogeneous diseases involving multiple systems with which patients may present with a wide range of clinical phenotypes. Clinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that was performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis.

Customizing carrier screening in the Chinese population: Insights from a 334-gene panel.

Objective: This study aimed to evaluate the yield and applicability of expanded carrier screening and propose carrier rate screening thresholds suitable for the Chinese population by comparing the current screening panel with the American College of Medical Genetics and Genomics recommended panel of 113 genes.

Methods: Using targeted next-generation sequencing, a customized panel with 334 genes was performed on 2168 individuals without clinical phenotypes for expanded carrier screening purpose. Variant interpretation followed the American College of Medical Genetics and Genomics guidelines.

Identification of a novel variant in a family with developmental and epileptic encephalopathies: a case report and literature review.

Developmental and epileptic encephalopathies (DEEs) are a group of heterogeneous neurodevelopmental diseases characterized mainly by developmental delay/intellectual disability and early-onset epilepsy. Researchers have identified variations in the gene (OMIM* 610044) as the cause of DEE type 57 (MIM# 617771). We report in this study a 46-year-old woman who presented with early-onset epilepsy, intellectual disability, hypertrichosis, coarse facial features, and short stature.

Maternal uniparental disomy for chromosome 6 in 2 prenatal cases with IUGR: case report and literature review.

Background: Uniparental disomy (UPD) is a rare genetic condition leading to potential disease risks. Maternal UPD of chromosome 6 upd(6)mat is exceptionally rare, with limited cases reported. This study reported two new cases of upd(6)mat and reviewed the literature of previous cases.

The clinical, myopathological, and genetic analysis of 155 Chinese mitochondrial ophthalmoplegia patients with mitochondrial DNA single large deletions.

Background: Progressive external ophthalmoplegia (PEO) is a common subtype of mitochondrial encephalomyopathy.

Objective: The study aimed to investigate the relationship between mitochondrial DNA (mtDNA) abnormalities, muscle pathology, and clinical manifestations in Chinese patients with single large-scale mtDNA deletion presenting with PEO.

Methods: This is a retrospective single-center study.

Expanding the mutational spectrum of ZTTK syndrome: A de novo variant with global developmental delay and malnutrition in a Chinese patient.

Background: Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, cortical malformations, epilepsy, visual problems, musculoskeletal abnormalities, and congenital malformations. ZTTK syndrome is caused by a heterozygous pathogenic variant of the SON gene (NM_138927) at chromosome 21q22.1.

Accurate Identification of Breakpoints in a Cryptic Reciprocal Translocation by Whole-Genome Sequencing.

Chromosomal abnormalities are a common cause of spontaneous abortions, but conventional detection methods (karyotype, FISH, and chromosomal microarray [CMA]) have limitations, and many cryptic balanced chromosomal rearrangements are difficult to detect. We describe a couple who experienced a missed abortion, studied by CMA. CMA of the abortion tissue detected a 1.

Case report: A novel mutation in 1 identified in a Chinese family with tricho-rhino-phalangeal syndrome I: A therapeutic challenge.

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant malformation caused by mutations involving the 1 gene. Patients with TRPS exhibit distinctive craniofacial and skeletal abnormalities. This report presents three intra-familial cases with 1 gene mutations that showed the characteristic features of TRPS.

Identification of TUBB8 Variants in 5 Primary Infertile Women with Multiple Phenotypes in Oocytes and Early Embryos.

Tubulin beta 8 class VIII (TUBB8) is a β-tubulin isotype that is specifically expressed in human oocytes and early embryos. It has been identified as a disease-causing gene in primary female infertility by affecting oocyte maturation arrest. This study investigated the genetic cause of female infertility in five patients from four families.

Clinical Utility of Medical Exome Sequencing: Expanded Carrier Screening for Patients Seeking Assisted Reproductive Technology in China.

Expanded carrier screening (ECS) is an effective method to identify at-risk couples (ARCs) and avoid birth defects. This study aimed to reveal the carrier spectrum in the Chinese population and to delineate an expanded carrier gene panel suitable in China. Medical exome sequencing (MES), including 4,158 disease-causing genes, was offered to couples at two reproductive centers.

Discovery of Novel Variants on the Gene: A Case Series of CHARGE Syndrome.

CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 () gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the genes and phenotypes.

Case Report: Report of Two Cases of Interstitial Lung Disease Caused by Novel Compound Heterozygous Variants in the Gene.

Interstitial lung disease (ILD) is a heterogeneous group of pulmonary disorders involving the lung interstitium and distal airways, also known as diffuse lung disease. The genetic defects resulting in alveolar surfactant protein dysfunction are a rare cause of ILD in pediatric patients. We report two unrelated pediatric patients with shortness of breath, dyspnea and hypoxemia, and the chest CT findings including patchy ground-glass opacity in both lung fields, suggestive of diffuse ILD.

Multisystem Mitochondrial Disease Associated With a Mare m.10000G>A Mitochondrial tRNA (MT-TG) Variant.

Background: Mitochondrial diseases are clinically heterogeneous, can occur at any age, and can manifest with a wide range of clinical symptoms. They can involve any organ or tissue, characteristically involve multiple systems, typically affecting organs that are highly dependent on aerobic metabolism, and making a definitive molecular diagnosis of a mitochondrial disorder is challenging.

Methods: Clinical data of the proband and his family members were gathered in a retrospective study.

Case Report: Be Aware of "New" Features of Niemann-Pick Disease: Insights From Two Pediatric Cases.

Niemann-Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann-Pick disease in infancy. The diagnosis is traditionally based on Niemann-Pick cells in bone marrow smears or liver biopsies.

Expanding the mutational spectrum of Rahman syndrome: A rare disorder with severe intellectual disability and particular facial features in two Chinese patients.

Background: The study aimed to investigate the clinical and genetic features of Rahman syndrome caused by HIST1H1E gene mutations.

Methods: We retrospectively analyzed the clinical information and genetic testing results of a Rahman syndrome family in an outpatient clinic in August 2020 and summarized the clinical characteristics of the HIST1H1E gene mutations in conjunction with peer-reviewed reports.

Results: A 4-year-old boy was diagnosed with severe developmental delay and with specific features (large head, full cheeks, high hairline, low-set ear, sparse eyebrows, and short neck) similar to his mother (mild intellectual disability, high hairline, reduced hair, ptosis, sagging skin, and hyperkeratosis) and premature aging.

Identification and Functional Characterization of a Novel Nonsense Variant in in a Southern Chinese Family With High Myopia.

has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES), we identified the first high myopia case with hemizygous -related mutation in a male patient in a Southern Chinese family. This novel truncated mutation (: c.

Missense mutation in gene caused psychomotor developmental delay and muscle weakness: A case report.

Background: The gene encodes a part of the dynamic protein, and the protein mutations may further affect the growth and development of neurons, resulting in degeneration of anterior horn cells of the spinal cord, and a variety of clinical phenotypes finally resulting in axonal Charcot-Marie-Tooth disease type 20 (CMT20), mental retardation 13 (MRD13) and spinal muscular atrophy with lower extremity predominant 1 (SMA-LED). The incidence of the disease is low, and it is difficult to diagnose, especially in children. Here, we report a case of gene mutation and review the related literature to improve the pediatrician's understanding of gene-related disease to make an early correct diagnosis and provide better services for children.

Kv3.1 channelopathy: a novel loss-of-function variant and the mechanistic basis of its clinical phenotypes.

Background: KCNC1 encodes Kv3.1, a subunit of the Kv3 voltage-gated potassium channels. It is predominantly expressed in inhibitory GABAergic interneurons and cerebellar neurons.

Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders.

Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases.

Exome-based preconception carrier testing for consanguineous couples in China.

Objective: To evaluate the utility of clinical exome sequencing (ES)-based carrier screening in Chinese consanguineous couples.

Methods: Consanguineous couples were screened for autosomal recessive (AR) disorders using the clinical ES of 5000 genes associated with human diseases.

Results: We recruited 14 couples who elected to have sequencing.

Mesenchymal stem cells from different sources show distinct therapeutic effects in hyperoxia-induced bronchopulmonary dysplasia in rats.

Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC-MSCs) and bone marrow (BM-MSCs). Amniotic fluid MSCs (AF-MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation.

Novel Mutations in the Gene for Mitochondrial Disease and Characteristics of Related Phenotypic Spectrum: The First Three Cases From China.

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms.

Case Report: Two Chinese Infants of Sengers Syndrome Caused by Mutations in Gene.

Sengers syndrome (OMIM #212350) is a rare autosomal recessive disorder due to mutations in acylglycerol kinase () gene. We report two cases that were diagnosed clinically and confirmed genetically. Both infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, and heart failure was the most severe manifestation.