Genetic Diseases, X-Linked ; Humans ; Nystagmus, Congenital

X-linked dystonia-parkinsonism (XDP) is an adult-onset debilitating neurodegenerative disorder presenting with motor and nonmotor symptoms. The treatment options for XDP are limited. We described a patient with XDP who underwent a unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy with a one-year follow-up. The patient reported an immediate improvement in his pain after the procedure. Compared to baseline, there was an improvement in his scores in the dystonia (31%), parkinsonism (35.1%), and activities of daily living (71%) subscales at 1-year follow up. The overall improvement at one year was 46%. There were no adverse events noted. Additional studies with larger sample size and follow-up would be needed to document its long-term safety and efficacy.
Dystonia 3, Torsion, X-Linked ; Dystonic Disorders ; Genetic Diseases, X-Linked

In addition to hearing impairment, syndromic hearing impairment is often accompanied by disorders of urinary, skeletal, muscular, nervous, and ocular systems. Genetic factors have shown to play an important role in the pathogenesis of deafness. Mutations of X-linked genes may cause syndromic hearing impairment. Gene mapping, linkage analysis and next-generation sequencing may facilitate delineation of the pathogenesis of X-linked syndromic hearing impairment. This article reviews recent progress in molecular genetic research on X-linked syndromic hearing impairment, which may shed light for the diagnosis and treatment of these diseases.
Genetic Diseases, X-Linked ; genetics ; Genetic Research ; Hearing Loss ; diagnosis ; genetics ; therapy ; Humans ; Molecular Biology

OBJECTIVE: To determine the carrier rate for common recessive genetic diseases in Chenzhou region in order to provide a reference for carrier screening in this region. METHODS: Targeted capture and high-throughput sequencing were carried out to detect potential variants of 79 genes associated with 88 recessive genetic diseases. Couples at risk were provided with prenatal diagnosis upon their subsequent pregnancies. RESULTS: A total of 1314 individuals were enrolled, among whom 355 (27.02%) were found to be carrier for at least one disease. The carrier rates for 8 diseases have exceeded 1%, with the most common two including thalassemia (11.72%, 154/1314) and autosomal recessive deafness (5.48%, 72/1314). Ten couples were found to be at risk for producing affected offspring. Among these, five females were carriers for X-linked recessive genetic diseases. Following genetic counseling, seven couples had accepted prenatal diagnosis, and 3 affected fetuses were diagnosed. CONCLUSION The disease types and pathogenic variants of Chenzhou region have differed from previously reported. Further research is required to validate the above finding with a larger populations.
Female ; Pregnancy ; Humans ; China ; Prenatal Diagnosis ; Fetus ; Genetic Counseling ; Genetic Diseases, X-Linked

OBJECTIVEX-linked spondyloepiphyseal dysplasia tarda (SEDL) is a rare osteochondrodysplasia caused by mutations of SEDL gene, which usually onset in late childhood without systemic complications. In this study, we have provided prenatal diagnosis for an affected family with a combined strategy including direct sequencing, fetal-sex identification and microsatellite linkage analysis.

METHODSTwo amniotic fluid samples from carrier gravida and 7 blood samples from individuals in this SEDL pedigree were obtained. Genomic DNA was extracted from the samples using standard phenol-chloroform method. SRY and AMEL genes were employed to assess fetal sex. Microsatellite DXS16 was genotyped for linkage analysis. A pathogenic mutation of the SEDL gene was identified by bi-directionally direct sequencing of the third exon as well as its exon/intron boundaries.

RESULTSTwo male fetuses were confirmed by fetal-sex assessment. The mutation of the SEDL gene was identified as a nucleotide substitution of the splice acceptor site in intron 2, IVS2-2A>C. DNA sequencing indicated that one fetus is hemizygote carrying the mutation, whilst another is not a carrier. Linkage analysis was identical with the sequencing results. Follow-up also confirmed the result of prenatal diagnosis.

CONCLUSIONFetal-sex assessment combined with microsatellite linkage analysis and bi-directionally direct sequencing is a more accurate and ready strategy for prenatal diagnosis of families affected with SEDL.

Genetic Diseases, X-Linked ; diagnosis ; Genetic Linkage ; Humans ; Male ; Osteochondrodysplasias ; diagnosis ; Prenatal Diagnosis ; Sequence Analysis, DNA

OBJECTIVE: Endoscopic third ventriculostomy (ETV) has been shown to be a sufficient alternative in the surgical treatment of hydrocephalus. Our goal in this retrospective study is to analyze our results with the use of ETV in our first 30 cases that it may provide us with selection criteria as to who among our patients will benefit most from this procedure.
METHODOLOGY: Thirty ETVs were performed in 30 patients. Their ages ranged from 2-155 months. Hydrocephalus was caused by aqueductal stenosis in 17 patients, tumors in 7, post-infectious in 3, Dandy-Walker malformation in 2 and arachnoid cyst in 1 patient. The outcome of ETV was evaluated in 26 of the cases that were available for follow-up
RESULTS: The overall success rate was 69.2 percent. Patients with non-communicating hydrocephalus from post-infectious causes, tumors and aqueductal stenosis had high success rates. Patients less than 6 months of age had a poor outcome. Complications included ventriculitis in 1 patient
CONCLUSION: ETV is a viable treatment option for non-communicating hydrocephalus secondary to post-infectious cause, aqueductal stenosis and tumors. A successful outcome is more likely if ETV is done in patients more than 6 months of age Patients who have previously undergone shunting and who have non-communicating hydrocephalus should undergo ETV at the time of shunt failure. These patients showed good outcome.

Human ; Male ; Female ; Infant ; Ventriculostomy ; Dandy-walker Syndrome ; Arachnoid Cysts ; Hydrocephalus, X-linked ; Hydrocephalus ; Cerebral Aqueduct ; Genetic Diseases, X-linked

This paper reviews the bipolar spectrum concept historically and empirically. It describes how the concept derives from Kraepelin, but was lost with DSM-III, which divided the broad manic-depressive illness concept, based on recurrent mood episodes of either polarity, to the bipolar versus unipolar dichotomy, based on allowing non-recurrent mood episodes of only one polarity. This approach followed the views of Karl Leonhard and other critics of Kraepelin. Thus post DSM-III American psychiatry is not neo-Kraepelinian, as many claim, but neo-Leonhardian. The bipolar spectrum approach, as advocated by Akiskal and Koukopoulos first, harkens back to the original broad Kraepelinian view of manic-depressive illness. The evidence for and against this approach is discussed, and common misconceptions, including mistaken claims that borderline personality is similar, are revealed and critiqued.
Bipolar Disorder ; Diagnostic and Statistical Manual of Mental Disorders ; Genetic Diseases, X-Linked

OBJECTIVE: To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations. METHODS: Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively. RESULTS: All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3 was decreased in 60.0% patients, CD19 was decreased in 12.0% patients, and CD56CD16 in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived. CONCLUSION WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.
Genetic Diseases, X-Linked ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies ; Thrombocytopenia ; Wiskott-Aldrich Syndrome Protein ; genetics

OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics* ; Creatine ; Genetic Testing ; Heterozygote ; Humans ; Mental Retardation, X-Linked ; Mutation

5-Aminolevulinate Synthetase/genetics* ; Anemia, Sideroblastic/genetics* ; Genetic Diseases, X-Linked/genetics* ; Humans ; Mutation