The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

Background: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated.

Objective: The objective of the study is to clarify the core features and influence factors of CRD patients in China.

Episodic Neurological Dysfunction in X-Linked Charcot-Marie-Tooth Disease: Expansion of the Phenotypic and Genetic Spectrum.

Background And Purpose: X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene () to extend the phenotypic and genetic description of CMTX1.

Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1.

Clinical heterogeneity in a family with flail arm syndrome and review of hnRNPA1-related spectrum.

Objective: Flail arm syndrome (FAS) is one of the atypical subtypes of amyotrophic lateral sclerosis (ALS). Mutations in hnRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare genetic cause of ALS. Herein, marked clinical heterogeneity of FAS in a pedigree with a known hnRNPA1 variant was described to raise early awareness of the ALS variant.

Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation in Gene: A Case Series.

Mutations in are known to cause Charcot-Marie-Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). In this study, we presented three patients with mutation in who were diagnosed with dHMN. Proband 1 was a 14-year-old male with progressive bilateral lower limb weakness and walking difficulty for four years.

Clinical and genetic analyses of 150 patients with paroxysmal kinesigenic dyskinesia.

Background: Mutations in PRRT2 and 16p11.2 microdeletion including PRRT2 have been identified as the pathogenic cause of paroxysmal kinesigenic dyskinesia (PKD).

Objective: The objective was to investigate the clinical and genetic features of PKD and to analyze the genotype-phenotype correlation.

Generation of an human induced pluripotent stem cell JTUi007-A from a patient with CSF1R-related leukoencephalopathy carrying heterozygous p.Ile794Thr mutation in CSF1R gene.

CSF1R-related leukoencephalopathy is an adult-onset monogenic microgliopathy causing leukoencephalopathy with high mortality and disabiliity. Here, an human induced pluripotent stem cell (hiPSC) line was generated from peripheral blood mononuclear cells of a 46-year-old female patient carrying heterozygous c.2381 T>C/p.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations.

Objective: We aimed to explore the potential causative gene for PKD.

Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome.

Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes.

Advances in hyperekplexia and other startle syndromes.

Startle, a basic alerting reaction common to all mammals, is described as a sudden involuntary movement of the body evoked by all kinds of sudden and unexpected stimulus. Startle syndromes are heterogeneous groups of disorders with abnormal and exaggerated responses to startling events, including hyperekplexia, stimulus-induced disorders, and neuropsychiatric startle syndromes. Hyperekplexia can be attributed to a genetic, idiopathic, or symptomatic cause.

A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease.

Alexander disease (AxD) is a cerebral white matter disease affecting a wide range of ages, from infants to adults. In the present study, two cases of bulbospinal form AxD were reported, and a preliminary exploration of AxD was conducted thorough clinical, functional magnetic resonance imaging (fMRI) and functional analyses. In total, two de novo mutations in the glial fibrillary acidic protein () gene (c.

Late-onset autoimmune polyendocrine syndrome type 1: a case report and literature review.

Autoimmune polyendocrine syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenic disorder, is classically characterized by a triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. The identified causative gene is autoimmune regulator (AIRE), which encodes a critical transcription factor and is essential for self-tolerance. Here, we describe a late-onset Chinese case who presented with symptoms of persistent tetany due to hypocalcemia.

Altered structural and functional connectivity in CSF1R-related leukoencephalopathy.

CSF1R-related leukoencephalopathy is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few studies have investigated the intrinsic brain alternations of patients with CSF1R-related leukoencephalopathy. We aim to evaluate the structural and functional changes in those patients.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

Background: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor.

Objectives: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy.

Excessive Startle with Novel Mutations in 4 Chinese Patients and a Literature Review of -Related Hyperekplexia.

Background And Purpose: Hyperekplexia (HPX), a rare neurogenetic disorder, is classically characterized by neonatal hypertonia, exaggerated startle response provoked by the sudden external stimuli and followed by a shortly general stiffness. Glycine receptor alpha 1 () is the major pathogenic gene of the disease. We described the clinical manifestations of genetically confirmed HPX patients and made a literature review of -related HPX to improve the early recognition and prompt the management of the disorder.

New phenotype of DCTN1-related spectrum: early-onset dHMN plus congenital foot deformity.

Objective: To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship.

Methods: Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atrophy. Patient 2 is a 48-year-old woman with adult-onset progressive weakness, lower limbs atrophy, and pyramid bundle signs.

Clinicopathologic characterization and abnormal autophagy of -related leukoencephalopathy.

Background: -related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor () gene mutation. Few of mutations have been functionally testified and the pathogenesis remains unknown.

Methods: In order to investigate clinical and pathological characteristics of patients with -related leukoencephalopathy and explore the potential impact of mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases.

Novel mutations in the SPAST gene cause hereditary spastic paraplegia.

Background: Mutations in the SPAST gene are the most frequent cause of hereditary spastic paraplegia (HSP). We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein.

Methods: Whole-exome sequencing (WES) combined with multiplex ligation-dependent probe amplification (MLPA) were performed in a cohort of 150 patients clinically diagnosed with HSP.

Primary familial brain calcification presenting as paroxysmal kinesigenic dyskinesia: Genetic and functional analyses.

Background: Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by calcium deposition in bilateral and symmetric brain. Evidence suggested that PFBC might be associated with paroxysmal kinesigenic dyskinesia (PKD). We aim to investigate the genetic causes in PFBC patients manifested as PKD, and further to explore the pathogenic impact of the identified mutations.

Lysosomal degradation of GMPPB is associated with limb-girdle muscular dystrophy type 2T.

Objective: GDP-mannose pyrophosphorylase B (GMPPB) related phenotype spectrum ranges widely from congenital myasthenic syndrome (CMS), limb-girdle muscular dystrophy type 2T (LGMD 2T) to severe congenital muscle-eye-brain syndrome. Our study investigates the clinicopathologic features of a patient with novel mutations and explores the pathogenetic mechanism.

Methods: The patient was a 22-year-old woman with chronic proximal limb weakness for 9 years without cognitive deterioration.

Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders.

Objectives: To describe the clinical and genetic features of a Chinese peroxisome biogenesis disorder 6B patient with PEX10 mutations and review PEX10-related peroxisomal disorders.

Patients And Methods: The proband is a 7-year-old boy with mild mental retardation and gait instability, intention tremor and nystagmus. An extensive clinical and laboratory evaluation including molecular genetic studies was performed.

The study of exercise tests in paroxysmal kinesigenic dyskinesia.

Objective: To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET).

Methods: Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects.