KLHL24 associated cardiomyopathy: Gene function to clinical management.

Background: KLHL24 (Kelch-like protein 24) is a significant component of the ubiquitin-proteasome system (UPS), involved in regulating protein turnover through targeted ubiquitination and degradation. Germline mutations in KLHL24 gene have been known to cause Epidermolysis Bullosa Simplex characterized by skin fragility but has recently been found to cause Cardiomyopathy.

Main Body: Various cardiomyopathies, including hypertrophic cardiomyopathy and dilated cardiomyopathy, leading to abnormal protein degradation and affecting the stability and function of essential cardiac proteins which finally results into structural and functional abnormalities in cardiac muscle.

The KCNB2 gene and its role in neurodevelopmental disorders: Implications for genetics and therapeutic advances.

Neurodevelopmental disorders (NDDs) are increasingly linked to genetic mutations that disrupt key neuronal processes. The KCNB2 gene encodes a crucial component of voltage-gated potassium channels, essential for regulating neuronal excitability and synaptic transmission. Mutations in KCNB2 typically alter potassium channel inactivation, leading to various NDDs, including autism spectrum disorders (ASD), intellectual disabilities (ID), and epilepsy.

SEPHS1 Gene: A new master key for neurodevelopmental disorders.

The SEPHS1 (Selenophosphate Synthetase 1) gene encodes a critical enzyme for synthesizing selenophosphate, the active donor of selenium (Se) necessary for selenoprotein biosynthesis. Selenoproteins are vital for antioxidant defense, thyroid hormone metabolism, and cellular homeostasis. Mutations in SEPHS1 gene, are associated with neurodevelopmental disorders with developmental delay, poor growth, hypotonia, and dysmorphic features.

Identification of a Novel Homozygous Mutation in Gene Causes Very Rare Charcot-Marie-Tooth Disease Type 4B1.

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot-Marie-Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance.

Identification and functional characterization of a novel heterozygous splice‑site mutation in the calpain 3 gene causes rare autosomal dominant limb‑girdle muscular dystrophy.

Limb-girdle muscular dystrophies are a group of extremely heterogenous neuromuscular disorders that manifest with gradual and progressive weakness of both proximal and distal muscles. Autosomal dominant limb-girdle muscular dystrophy (LGMDD4) or calpainopathy is a very rare form of myopathy characterized by weakness and atrophy of both proximal and distal muscles with a variable age of onset. LGMDD4 is caused by germline heterozygous mutations of the calpain 3 ( gene.

Whole-exome sequencing identified a homozygous novel mutation in a child with omenn syndrome.

Introduction And Objectives: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymph-adenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human gene cause OS.

Whole exome sequencing identified a homozygous novel mutation in SUOX gene causes extremely rare autosomal recessive isolated sulfite oxidase deficiency.

Background: Isolated sulfite oxidase deficiency (ISOD) is a rare type of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. Germline mutation in SUOX gene causes ISOD. Till date, only 32 mutations of SUOX gene have been identified and reported to be associated with ISOD.

Genetic Profiles and Three-year Follow-up Study of Chinese Males With Congenital Hypogonadotropic Hypogonadism.

Background: The correlation between long-term treatment outcomes with genotypes in congenital hypogonadotropic hypogonadism (CHH) males is rarely reported.

Aim: To investigate the correlations among genotypes, phenotypes, and treatment outcomes for CHH male patients.

Methods: Whole exome sequencing was performed for 73 Chinese CHH males from one academic center.

Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer.

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30).

KVarPredDB: a database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses.

Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16, and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists.

Family-Based Whole Genome Sequencing Identified Novel Variants in ABCA5 Gene in a Patient with Idiopathic Ventricular Tachycardia.

Idiopathic ventricular tachycardia (IVT) is the major cause of sudden cardiac death. Patients with IVT were usually manifested without structural heart disease. In this present study, we performed family-based whole genome sequencing (WGS) and Sanger sequencing for a 5-year-old Chinese boy with IVT and all the unaffected family members in order to identify the candidate gene and disease-causing mutation underlying the disease phenotype.

Identification and functional characterization of mutations in LPL gene causing severe hypertriglyceridaemia and acute pancreatitis.

Hypertriglyceridaemia is a very rare disorder caused by the mutations of LPL gene, with an autosomal recessive mode of inheritance. Here, we identified two unrelated Chinese patients manifested with severe hypertriglyceridaemia and acute pancreatitis. The clinical symptoms of proband 1 are more severe than proband 2.

A comprehensive assessment of Next-Generation Sequencing variants validation using a secondary technology.

Background: Recently, increasing innovations improved the accuracy of next generation sequencing (NGS) data. However, the validation of all NGS variants increased the cost and turn-around time of clinical diagnosis, and therefore limited the further development of clinical applications. We aimed to comprehensively assess the necessity of validating NGS variants.

Novel loss-of-function mutation in gene identified in a Chinese female with a family history of ovarian cancer: A case report.

Inherited loss-of-function mutations in the tumor suppressor gene are associated with a high risk of ovarian cancer in the Chinese population. The current case report discusses a novel heterozygous insertion in gene, c.3195_3196insA, in a 54-year-old Chinese female with hereditary ovarian cancer.

Targeted Next Generation Sequencing Revealed a Novel Homozygous Mutation in Gene Causes Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in a Chinese Family.

Hereditary hearing impairment is one of the major and common birth defects in Chinese population. Non-syndromic sensorineural hearing loss (NSHL) is the most common types of hereditary hearing impairment. Genotypically and phenotypically NSHL is extremely heterogenous and follow either autosomal dominant or autosomal recessive or X-linked mode of inheritance.

A Novel Initiation Codon Mutation (c.3G>T) in a Large Chinese Lynch Syndrome Family with Different Onset Age and mRNA Expression Level.

Lynch syndrome is a genetically and clinically heterogeneous disorder; it is caused by a germline mutation in DNA mismatch repair (MMR) genes. Individuals with a heterozygous mutation in MLH1 have an increased risk for developing colorectal cancer. Here we described a 5-generation Chinese Lynch syndrome family with different severity and onset age.

Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy-dystroglycanopathy.

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 (MDDGC9) is the rarest type of autosomal recessive muscular dystrophies. MDDGC9 is manifested with an early onset in childhood. Patients with MDDGC9 usually identified with defective glycosylation of DAG1, hence it is known as "dystroglycanopathies".

Identification of a novel breast cancer-causing mutation in the gene by targeted next generation sequencing: A case report.

Hereditary breast cancer is an autosomal dominant syndrome caused by germ-line mutations in the human breast cancer genes, and . Mutations in either or are the major causes of familial and early-onset breast cancer. The present study investigated a 33-year-old Chinese female patient with breast cancer using targeted next generation sequencing.

Whole Exome Sequencing Identified a Novel Heterozygous Mutation in Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia.

Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of gene causes AIP. Mutation of gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase.