A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.

Elife. 2016 Dec 21;5:

Authors: Mathew RS, Tatarakis A, Rudenko A, Johnson-Venkatesh EM, Yang YJ, Murphy EA, Todd TP, Schepers ST, Siuti N, Martorell AJ, Falls WA, Hammack SE, Walsh CA, Tsai LH, Umemori H, Bouton ME, Moazed D

Abstract
The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.

PMID: 28001126 [PubMed - indexed for MEDLINE]

Anaesthesia and orphan disease: airway and anaesthetic management in Huntington's disease.

BMJ Case Rep. 2017 Oct 19;2017:

Authors: Nguyen PT, Meeks D, Liotiri D

Abstract
We present a case that highlights the issues surrounding the delivery of a safe general anaesthetic to a patient with Huntington's disease (HD) and bulbar dysfunction. In the case of a 46-year-old patient undergoing laparoscopic percutaneous endoscopic gastrostomy tube insertion, we discuss the rationale behind our chosen method and anaesthetic agents as well as airway issues specific to HD. In a patient whose condition would not allow for an awake fibreoptic intubation, we opted for a modified rapid sequence induction. Special considerations were made with regard to muscle relaxation given the complications associated with inadequate paralysis and reversal in patients with HD. The technique we describe may also apply to other patient categories, such as patients with movement disorders, bulbar dysfunction and dementia.

PMID: 29054944 [PubMed - in process]

Will the RACE for Children Act lead to new treatments for pediatric cancer?

Cancer. 2017 01 01;123(2):189

Authors: Fink JL

PMID: 28067946 [PubMed - indexed for MEDLINE]

Long-term effects of systemic gene therapy in a canine model of myotubular myopathy.

Muscle Nerve. 2017 Nov;56(5):943-953

Authors: Elverman M, Goddard MA, Mack D, Snyder JM, Lawlor MW, Meng H, Beggs AH, Buj-Bello A, Poulard K, Marsh AP, Grange RW, Kelly VE, Childers MK

Abstract
INTRODUCTION: X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years.
METHODS: We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression.
RESULTS: Four years following AAV-mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV-infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength.
CONCLUSIONS: AAV-mediated gene transfer of MTM1 in young XLMTM dogs results in long-term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943-953, 2017.

PMID: 28370029 [PubMed - indexed for MEDLINE]

Nance-Horan syndrome-The oral perspective on a rare disease.

Am J Med Genet A. 2017 Jan;173(1):88-98

Authors: Gjørup H, Haubek D, Jacobsen P, Ostergaard JR

Abstract
The present study describes seven patients with Nance-Horan syndrome, all referred to a specialized oral care unit in the Central Denmark Region. A literature search on "Nance Horan Syndrome" resulted in 53 publications among which 29 reported on dental findings. Findings reported in these papers have been systematized to obtain an overview of the reported findings and the terminology on dental morphology. All seven patients included in the present study showed deviations of crown morphology on incisors and/or molars. The only consistent and very clear dental aberration was alterations in the tooth morphology that is screwdriver-shaped incisors and bud molars being most pronounced in the permanent dentition, but were also present in the primary dentition. In addition, three patients had supernumerary teeth, and three had dental agenesis. In conclusion, a dental examination as a part of the diagnostic process may reveal distinct characteristics of the dental morphology, which could be of diagnostic value and facilitate an early diagnosis. In the description of molar morphology in NHS patients, it is recommended to use the term "bud molar." The combination of congenital cataract, screwdriwer-shaped incisors and bud-shaped molars is a strong clinical indication of Nance-Horan syndrome. © 2016 Wiley Periodicals, Inc.

PMID: 27616609 [PubMed - indexed for MEDLINE]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/10/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

DIGNiFI: Discovering causative genes for orphan diseases using protein-protein interaction networks.

BMC Syst Biol. 2017 Mar 14;11(Suppl 3):23

Authors: Liu X, Yang Z, Lin H, Simmons M, Lu Z

Abstract
BACKGROUND: An orphan disease is any disease that affects a small percentage of the population. Orphan diseases are a great burden to patients and society, and most of them are genetic in origin. Unfortunately, our current understanding of the genes responsible for inherited orphan diseases is still quite limited. Developing effective computational algorithms to discover disease-causing genes would help unveil disease mechanisms and may enable better diagnosis and treatment.
RESULTS: We have developed a novel method, named as DIGNiFI (Disease causIng GeNe FInder), which uses Protein-Protein Interaction (PPI) network-based features to discover and rank candidate disease-causing genes. Specifically, our approach computes topologically similar genes by taking into account both local and global connected paths in PPI networks via Direct Neighbors and Local Random Walks, respectively. Furthermore, since genes with similar phenotypes tend to be functionally related, we have integrated PPI data with gene ontology (GO) annotations and protein complex data to further improve the performance of this approach. Results of 128 orphan diseases with 1184 known disease genes collected from the Orphanet show that our proposed methods outperform existing state-of-the-art methods for discovering candidate disease-causing genes. We also show that further performance improvement can be achieved when enriching the human-curated PPI network data with text-mined interactions from the biomedical literature. Finally, we demonstrate the utility of our approach by applying our method to identifying novel candidate genes for a set of four inherited retinal dystrophies. In this study, we found the top predictions for these retinal dystrophies consistent with literature reports and online databases of other retinal dystrophies.
CONCLUSIONS: Our method successfully prioritizes orphan-disease-causative genes. This method has great potential to benefit the field of orphan disease research, where resources are scarce and greatly needed.

PMID: 28361678 [PubMed - indexed for MEDLINE]

Nursing Management of Advanced Merkel Cell Carcinoma.

Oncol Nurs Forum. 2016 Nov 01;43(6):680-683

Authors: Lowry PA, Freeman ML, Russell JS

Abstract
Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

PMID: 27768129 [PubMed - indexed for MEDLINE]

Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis.

Liver Transpl. 2016 Sep;22(9):1245-53

Authors: Amir AZ, Ling SC, Naqvi A, Weitzman S, Fecteau A, Grant D, Ghanekar A, Cattral M, Nalli N, Cutz E, Kamath B, Jones N, De Angelis M, Ng V, Avitzur Y

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease, characterized by overwhelming stimulation of the immune system and categorized as primary or secondary types. Occasionally, acute liver failure (ALF) may dominate the clinical presentation. Given the systemic nature of HLH and risk of recurrence, HLH is considered by many a contraindication to liver transplantation (LT). The aim of this study is to review our single-center experience with LT in children with secondary HLH and ALF (HLH-ALF). This is a cross-sectional, retrospective study of children with secondary HLH-ALF that underwent LT in 2005-2014. Of 246 LTs, 9 patients (3 males; median age, 5 years; range, 0.7-15.4 years) underwent LT for secondary HLH-ALF. Disease progression was rapid with median 14 days (range, 6-27 days) between first symptoms and LT. Low fibrinogen/high triglycerides, elevated ferritin, hemophagocytosis on liver biopsy, and soluble interleukin 2 receptor levels were the most commonly fulfilled diagnostic criteria; HLH genetic studies were negative in all patients. Immunosuppressive therapy after LT included corticosteroids adjusted to HLH treatment protocol and tacrolimus. Thymoglobulin (n = 5), etoposide (n = 4), and alemtuzumab (n = 2) were used in cases of recurrence. Five (56%) patients experienced HLH recurrence, 1 requiring repeat LT, and 3 died. Overall graft and patient survival were 60% and 67%, respectively. Six patients are alive and well at a median of 24 months (range, 15-72 months) after transplantation. In conclusion, LT can be beneficial in selected patients with secondary HLH-ALF and can restore good health in an otherwise lethal condition. Liver Transplantation 22 1245-1253 2016 AASLD.

PMID: 27216884 [PubMed - indexed for MEDLINE]

Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1.

J Clin Endocrinol Metab. 2017 Sep 01;102(9):3546-3556

Authors: Orlova EM, Sozaeva LS, Kareva MA, Oftedal BE, Wolff ASB, Breivik L, Zakharova EY, Ivanova ON, Kämpe O, Dedov II, Knappskog PM, Peterkova VA, Husebye ES

Abstract
Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare.
Objective: To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort.
Subjects and Methods: Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing.
Results: We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21).
Conclusions: The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.

PMID: 28911151 [PubMed - indexed for MEDLINE]

AcroangiodermatitisA Presentation of Two Cases of Nonhealing Ulcerations in the Lower Extremity.

J Am Podiatr Med Assoc. 2016 Sep 02;106(5):364-369

Authors: Hronek AL, Clark SN, Young G, Kinikini D, Wells J

Abstract
Acroangiodermatitis (AAD), also known as pseudo-Kaposi's sarcoma, is an uncommon benign angioproliferative condition most commonly seen in the lower extremities. This condition often presents as discolored patches that progress to painful ulcerations. The list of vascular conditions associated with this diagnosis is vast. Acroangiodermatitis presents similarly to more aggressive conditions such as Kaposi's sarcoma, making histopathologic examination helpful in its diagnosis. We present two cases of AAD in the setting of chronic venous insufficiency.

PMID: 27762609 [PubMed - indexed for MEDLINE]

Palatal Perforation as a Rare Complication of Nasal Septoplasty.

Aesthetic Plast Surg. 2016 Dec;40(6):850-853

Authors: Tilaveridis I, Kalaitsidou I, Kyrgidis A, Astreidis IS

Abstract
BACKGROUND: Nasal septoplasty is one of the most commonly performed surgical procedures by otolaryngologists or plastic surgeons and is generally performed to improve the quality of life. Although nasal surgeries are generally safe and effective procedures, various complications have been described in the literature.
METHODS: In this article, we present a rare case of fracture of a part of the hard palate resulting in palatal perforation after nasal septoplasty surgery early diagnosed and successfully treated.
RESULTS: Patient follow-up 1 year after oronasal closure revealed complete healing of the hard palate without the presence of fistula.
CONCLUSIONS: Palatal perforation during septoplasty is extremely rare and, even though it is not a life-threatening complication, has potentially annoying effects; according to its size, it can result in nasal speech, oral health problems, and nasal regurgitation of liquids and is sometimes related with reconstructive challenging problems.
LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors. www.springer.com/00266 .

PMID: 27631545 [PubMed - indexed for MEDLINE]

Primary mitral valve sarcoma: multimodality imaging and therapy.

Eur Heart J Cardiovasc Imaging. 2016 Oct;17(10):1137

Authors: Barber H, Menezes L, Dileo P, Lloyd G, Bhattacharyya S

PMID: 27369847 [PubMed - indexed for MEDLINE]

Kyasanur Forest Disease (KFD): Rare Disease of Zoonotic Origin.

J Nepal Health Res Counc. 2016 Sep;14(34):214-218

Authors: Muraleedharan M

Abstract
Kyasanur forest disease (KFD) is a rare tick borne zoonotic disease that causes acute febrile hemorrhagic illness in humans and monkeys especially in southern part of India. The disease is caused by highly pathogenic KFD virus (KFDV) which belongs to member of the genus Flavivirus and family Flaviviridae. The disease is transmitted to monkeys and humans by infective tick Haemaphysalisspinigera. Seasonal outbreaks are expected to occur during the months of January to June. The aim of this paper is to briefly summarize the epidemiology, mode of transmission of KFD virus, clinical findings, diagnosis, treatment, control and prevention of the disease..

PMID: 28327690 [PubMed - indexed for MEDLINE]

Rare and difficult to treat haematological diseases.

Lancet Haematol. 2015 Jan;2(1):e1

Authors:

PMID: 26687422 [PubMed - indexed for MEDLINE]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/10/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/10/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Systemic Manifestations in Pyridox(am)ine 5'-Phosphate Oxidase Deficiency.

Pediatr Neurol. 2017 Jun 03;:

Authors: Guerriero RM, Patel AA, Walsh B, Baumer FM, Shah AS, Peters JM, Rodan LH, Agrawal PB, Pearl PL, Takeoka M

Abstract
OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5'-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5'-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5'-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5'-phosphate oxidase deficiency.
METHODS: A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5'-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations.
RESULTS: Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674 G>T, c.686 G>A and c.352G>A).
CONCLUSION: In addition to the well-described epileptic encephalopathy, pyridox(am)ine 5'-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.

PMID: 28985901 [PubMed - as supplied by publisher]

Fateful imprints.

Science. 2017 Jan 13;355(6321):122-125

Authors: Couzin-Frankel J

PMID: 28082544 [PubMed - indexed for MEDLINE]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/10/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.