Read by QxMD icon Read

Genetic disorder

M S Mendonça, P M Mangiavacchi, P F De Sousa, J A S Crippa, A V Mendes, S R Loureiro, R Martín-Santos, C R Quirino, M M Kanashiro, A F L Rios
BACKGROUND: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life...
November 6, 2018: Journal of Affective Disorders
Hua Yang, Kequan Li, Song Han, Ailing Zhou, Zhaolan Joe Zhou
Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality. Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate. The seemingly simple genetic root and the availability of genetic data from RTT patients have led to the generation and characterization of a series of mouse models recapitulating RTT-associated genetic mutations...
November 14, 2018: Neurobiology of Learning and Memory
Yassmin Mansela Musthaffa, Vikas Goyal, Margaret-Anne Harris, Nitin Kapur, Juliane Leger, Mark Harris
Background Congenital central hypoventilation syndrome (CCHS) is a rare disorder of autonomic control. A hypoglycaemic seizure in a 4-year-old girl with CCHS led to a more detailed examination of glycaemic control in a cohort of children with CCHS. Methods We conducted an observational cohort study of glucose homeostasis in seven children (3 months to 12 years) with genetically confirmed CCHS using a combination of continuous glucose monitoring (CGM), fasting studies and oral glucose tolerance test (OGTT). CGM was used to compare the effect of diazoxide and dietary intervention in the index patient...
November 17, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
Mark A Reimers, Carl Craver, Mikhail Dozmorov, Silviu-Alin Bacanu, Kenneth S Kendler
Genome wide association studies (GWAS) for behavioral traits and psychiatric disorders have inspired both confident optimism and withering criticism. Although many recent findings from well powered GWAS have been replicated in independent data sets, the genes identified have pinned down few if any underlying causal mechanisms. Therefore, a key issue is whether or not the genes implicated by GWAS form a coherent story on their own and thus could in principle lead to insight into the biological mechanisms underlying the trait or disorder...
November 16, 2018: Behavior Genetics
Cindy Bokobza, Juliette Van Steenwinckel, Shyamala Mani, Valérie Mezger, Bobbi Fleiss, Pierre Gressens
Genetic anomalies have a role in autism spectrum disorders (ASD). Each genetic factor is responsible for a small fraction of cases. Environment factors, like preterm delivery, have an important role in ASD. Preterm infants have a 10-fold higher risk of developing ASD. Preterm birth is often associated with maternal/fetal inflammation, leading to a fetal/neonatal inflammatory syndrome. There are demonstrated experimental links between fetal inflammation and the later development of behavioral symptoms consistent with ASD...
November 16, 2018: Pediatric Research
Diarra K Williams, Carlos Pinzón, Shannon Huggins, Jane H Pryor, Alyssa Falck, Forrest Herman, James Oldeschulte, Michael B Chavez, Brian L Foster, Sarah H White, Mark E Westhusin, Larry J Suva, Charles R Long, Dana Gaddy
The availability of tools to accurately replicate the clinical phenotype of rare human diseases is a key step toward improved understanding of disease progression and the development of more effective therapeutics. We successfully generated the first large animal model of a rare human bone disease, hypophosphatasia (HPP) using CRISPR/Cas9 to introduce a single point mutation in the tissue nonspecific alkaline phosphatase (TNSALP) gene (ALPL) (1077 C > G) in sheep. HPP is a rare inherited disorder of mineral metabolism that affects bone and tooth development, and is associated with muscle weakness...
November 16, 2018: Scientific Reports
Ting Zhou, Tae Wan Kim, Chi Nok Chong, Lei Tan, Sadaf Amin, Zohreh Sadat Badieyan, Suranjit Mukherjee, Zaniar Ghazizadeh, Hui Zeng, Min Guo, Miguel Crespo, Tuo Zhang, Reyn Kenyon, Christopher L Robinson, Effie Apostolou, Hui Wang, Jenny Zhaoying Xiang, Todd Evans, Lorenz Studer, Shuibing Chen
Common disorders, including diabetes and Parkinson's disease, are caused by a combination of environmental factors and genetic susceptibility. However, defining the mechanisms underlying gene-environment interactions has been challenging due to the lack of a suitable experimental platform. Using pancreatic β-like cells derived from human pluripotent stem cells (hPSCs), we discovered that a commonly used pesticide, propargite, induces pancreatic β-cell death, a pathological hallmark of diabetes. Screening a panel of diverse hPSC-derived cell types we extended this observation to a similar susceptibility in midbrain dopamine neurons, a cell type affected in Parkinson's disease...
November 16, 2018: Nature Communications
Sahar I Da'as, Khalid Fakhro, Angelos Thanassoulas, Navaneethakrishnan Krishnamoorthy, Alaaeldin Saleh, Brian Lewis Calver, Bared Safieh-Garabedian, Egon Toft, George Nounesis, F Anthony Lai, Michail Nomikos
The most common inherited cardiac disorder, hypertrophic cardiomyopathy (HCM), is characterized by thickening of heart muscle, for which genetic mutations in cardiac myosin-binding protein C3 ( c-MYBPC3 ) gene, is the leading cause. Notably, patients with HCM display a heterogeneous clinical presentation, onset and prognosis. Thus, delineating the molecular mechanisms that explain how disparate c-MYBPC3 variants lead to HCM is essential for correlating the impact of specific genotypes on clinical severity. Herein, five c-MYBPC3 missense variants clinically associated with HCM were investigated; namely V1 (R177H), V2 (A216T), V3 (E258K), V4 (E441K) and double mutation V5 (V3+V4), all located within the C1 & C2 domains of MyBP-C, a region known to interact with sarcomeric protein, actin...
November 16, 2018: Biochemical Journal
San San Xu, Paschal K Alexander, Yenni Lie, Vincent Dore, Svetlana Bozinovski, Rachel S Mulligan, Kenneth Young, Victor L Villemagne, Christopher C Rowe
OBJECTIVES: To further validate the diagnostic utility of 18 F-AV-133 vesicular monoamine transporter type 2 (VMAT2) positron emission tomography (PET) in patients with clinically uncertain parkinsonian syndromes (CUPS) by comparison to clinical diagnosis at 3 years follow-up. DESIGN, SETTING AND PARTICIPANTS: In a previous study, we reported that 18 F-AV-133 PET in community patients with CUPS changed diagnosis and management and increased diagnostic confidence...
November 15, 2018: BMJ Open
Alan M Smith, Joseph J King, Paul R West, Michael A Ludwig, Elizabeth L R Donley, Robert E Burrier, David G Amaral
BACKGROUND: Autism spectrum disorder (ASD) is behaviorally and biologically heterogeneous and likely represents a series of conditions arising from different underlying genetic, metabolic, and environmental factors. There are currently no reliable diagnostic biomarkers for ASD. Based on evidence that dysregulation of branched-chain amino acids (BCAAs) may contribute to the behavioral characteristics of ASD, we tested whether dysregulation of amino acids (AAs) was a pervasive phenomenon in individuals with ASD...
September 6, 2018: Biological Psychiatry
Kyu Young Lee, Yong Min Ahn, Se Hyun Kim, Hee-Gyoo Kang, Eun-Jeong Joo
BACKGROUND: A circadian rhythm disturbance is one of the essential components of the phenotype of bipolar disorder. It has been reported that casein kinase 1 epsilon (CSNK1E), a member of the clock gene family, is associated with psychiatric phenotypes. OBJECTIVES: We performed a genetic association study to determine the genetic role of CSNK1E in bipolar disorder and circadian rhythm disturbances in the Korean population. METHODS: The present study included 215 patients with bipolar disorder and 773 controls...
November 16, 2018: Nordic Journal of Psychiatry
Joanna S Amberger, Carol A Bocchini, Alan F Scott, Ada Hamosh
For over 50 years Mendelian Inheritance in Man has chronicled the collective knowledge of the field of medical genetics. It initially cataloged the known X-linked, autosomal recessive and autosomal dominant inherited disorders, but grew to be the primary repository of curated information on both genes and genetic phenotypes and the relationships between them. Each phenotype and gene is given a separate entry assigned a stable, unique identifier. The entries contain structured summaries of new and important information based on expert review of the biomedical literature...
November 16, 2018: Nucleic Acids Research
Martha Zakrzewski, Lisa A Simms, Allison Brown, Mark Appleyard, James Irwin, Nicola Waddell, Graham L Radford-Smith
Background and aims: This study aimed to characterise the mucosa-associated microbiota in ileal Crohn's disease (CD) patients and in healthy controls in terms of host genotype and inflammation status. Methods: The mucosa-associated microbiota of intestinal pinch biopsies from 15 ileal CD patients with mild and moderate disease and from 58 healthy controls were analysed by 16S ribosomal sequencing to determine microbial profile differences between (1) IL23R, NOD2 and ATG16L1 genotypes in healthy subjects, (2) ileal CD patients and control subjects, and (3) inflamed and non-inflamed mucosal tissue in CD patients...
November 16, 2018: Journal of Crohn's & Colitis
Jiayuan Xu, Qiaojun Li, Wen Qin, Mulin Jun Li, Chuanjun Zhuo, Huaigui Liu, Feng Liu, Junping Wang, Gunter Schumann, Chunshui Yu
Depression increases the conversion risk from amnestic mild cognitive impairment to Alzheimer's disease with unknown mechanisms. We hypothesize that the cumulative genomic risk for major depressive disorder may be a candidate cause for the increased conversion risk. Here, we aimed to investigate the predictive effect of the polygenic risk scores of major depressive disorder-specific genetic variants (PRSsMDD) on the conversion from non-depressed amnestic mild cognitive impairment to Alzheimer's disease, and its underlying neurobiological mechanisms...
November 14, 2018: Brain: a Journal of Neurology
Audrey Putoux, Dominique Baas, Marie Paschaki, Laurette Morlé, Charline Maire, Tania Attié-Bitach, Sophie Thomas, Bénédicte Durand
Acrocallosal syndrome (ACLS) is a rare genetic disorder characterized by agenesis or hypoplasia of corpus callosum (CC), polydactyly, craniofacial dysmorphism and severe intellectual deficiency. We previously identified KIF7, a key ciliary component of the Sonic hedgehog pathway, as being a causative gene for this syndrome, thus including ACLS in the group of ciliopathies. In both humans and mice, KIF7 depletion leads to abnormal GLI3 processing and over-activation of SHH target genes. To understand the pathological mechanisms involved in CC defects in this syndrome, we took advantage of a previously described Kif7-/- mouse model todemonstrate that in addition to polydactyly and neural tube closure defects, these mice present CC agenesis with characteristic Probst bundles, thus recapitulating major ACLS features...
November 15, 2018: Human Molecular Genetics
Stacey J Winham, William V Bobo, Jiajia Liu, Brandon Coombes, Lena Backlund, Mark A Frye, Joanna M Biernacka, Martin Schalling, Catharina Lavebratt
BACKGROUND: Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder...
November 3, 2018: Journal of Affective Disorders
Cecilia Mancini, Andrea Zonta, Giovanni Botta, Andrea Breda Klobus, Stefano Valbonesi, Barbara Pasini, Elisa Giorgio, Elsa Viora, Alfredo Brusco, Alessandro Brussino
Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by recessive mutations in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), variably associated with long bone hypoplasia, horseshoe kidney, venous anomalies, vertebral anomalies, developmental delay, and intellectual disability. Here, we report the case of a woman who interrupted her pregnancy after ultrasound scans revealed a depression of the frontal bone, posterior fossa anomalies, cerebral ventricular enlargement, cleft spine involving the sacral and lower-lumbar vertebrae, and bilateral microphthalmia...
November 13, 2018: European Journal of Medical Genetics
Charles J Glueck, Naila Goldenberg
Polycystic ovary syndrome (PCOS) has multiple etiologies including ovarian and adrenal hyperandrogenism, neuro-endocrine and hypothalamic-pituitary dysfunction, and disorders of peripheral insulin resistance. Obesity is neither necessary nor sufficient for the PCOS phenotype, and the association of PCOS with obesity is not universal, with national, cultural, and ethnic differences. Obesity, particularly visceral adiposity which is common in obese and non-obese women with PCOS, amplifies and worsens all metabolic and reproductive outcomes in PCOS...
November 13, 2018: Metabolism: Clinical and Experimental
Sina A Gharib, Ryan S McMahan, William E Eddy, Matthew E Long, William C Parks, Moira L Aitken, Anne M Manicone
BACKGROUND: Macrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma. OBJECTIVE: To examine the transcriptional and functional significance of macrophage repolarization from an "M1" towards an "M2" phenotype, and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation. METHODS: Monocyte-derived macrophages were collected from healthy and CF subjects and polarized to an M2 state using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin...
November 13, 2018: Journal of Allergy and Clinical Immunology
Jorge Rendon, Yesica Zuluaga, Lina Velilla, Jhon Ochoa, Joseph F Arboleda-Velasquez, Andrew Budson, Francisco Lopera, Yakeel T Quiroz
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder and is caused by mutations of the NOTCH3 gene. Cognitive decline in CADASIL is characterized by early impairments of attention, memory, and executive functions. Studying asymptomatic individuals with CADASIL offers a unique genetic model to understand preclinical vascular cognitive impairment and dementia. This study aimed at examine whether early preclinical physiological changes could be observed in asymptomatic individuals with CADASIL, who will go on to develop vascular cognitive impairment and dementia later in life...
November 13, 2018: Brain Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"