6 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 2017/06/06

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.

An Adult Case of Chromosome 22q11.2 Deletion Syndrome Associated with a High-positioned Right Aortic Arch.

Intern Med. 2017;56(7):865-872

Authors: Hoshino Y, Machida M, Shimano SI, Taya T

Abstract
Chromosome 22q11.2 deletion syndrome (22q11.2 DS) has a very wide phenotypic spectrum that includes dysmorphic features, cardiac anomalies, and hypocalcemia arising from hypoparathyroidism. We herein describe an adult case of 22q11.2 DS with associated hypoparathyroidism and anomalies of the aortic arch. Because the patient had been diagnosed with primary hypoparathyroidism at another hospital, a diagnosis of 22q11.2 DS had been overlooked. A chest X-ray examination revealed widening of the mediastinum caused by a high-positioned right aortic arch, and we subsequently confirmed a diagnosis of 22q11.2 DS using fluorescence in situ hybridization. Because primary hypoparathyroidism is a rare disorder, physicians should be aware of the variable phenotypic features of 22q11.2 DS.

PMID: 28381757 [PubMed - indexed for MEDLINE]

Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder.

Arq Neuropsiquiatr. 2017 Feb;75(2):92-95

Authors: Fragoso YD, Adoni T, Brooks JB, Gomes S, Goncalves MV, Jovem CL, Matta AP, Oliveira JF, Siquinelli F, Tauil CB, Troiani GN, Wille PR

Abstract
Methods: Series of cases collected from Brazilian centers.
Results: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset.
Conclusion: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

PMID: 28226077 [PubMed - indexed for MEDLINE]

Developmentally-Faithful and Effective Human Erythropoiesis in Immunodeficient and Kit Mutant Mice.

Am J Hematol. 2017 May 31;:

Authors: Fiorini C, Abdulhay NJ, McFarland SK, Munschauer M, Ulirsch JC, Chiarle R, Sankaran VG

Abstract
Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. This article is protected by copyright. All rights reserved.

PMID: 28568895 [PubMed - as supplied by publisher]

A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia. Predicted structure and function consequences.

Hamostaseologie. 2016 Nov 08;36(Suppl. 2):S34-S38

Authors: Ivaškevičius V, Rühl H, Detarsio G, Biswas A, Gupta S, Davoli M, Quartara A, Pérez S, Raviola M, Oldenburg J

Abstract
Afibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function.
PATIENTS AND METHODS: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico.
RESULTS: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta-chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain.
CONCLUSIONS: The novel missense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.

PMID: 27824214 [PubMed - indexed for MEDLINE]

Abdominal Pain due to a Wandering Liver.

J Gastrointest Surg. 2017 May;21(5):923-925

Authors: Bruneau A, Sandri GBL, Rayar M, Sulpice L, Boudjema K

Abstract
Wandering liver syndrome is an extremely rare congenital disorder. It is mainly diagnosed within the first years of life. Herein we report the case of a 40-year-old woman with hepatoptosis due to the absence of anatomical peritoneal attachments of the liver. Surgical treatment consisted in inserting the floppy right lobe of the liver in a subphrenic retroperitoneal pouch. This original technique provided excellent postoperative result.

PMID: 27659790 [PubMed - indexed for MEDLINE]

Pyoderma gangrenosum-like oral ulcerations in an elderly patient.

Gerodontology. 2015 Dec;32(4):309-13

Authors: Kaomongkolgit R, Subbalekha K, Sawangarun W, Thongprasom K

Abstract
OBJECTIVE: To present a case of pyoderma gangrenosum (PG)-like oral ulcerations in an elderly patient.
BACKGROUND: PG is an uncommon idiopathic, ulcerative, chronic inflammatory cutaneous disorder of unknown etiology, which is associated with systemic diseases found in more than 50% of patients. Oral lesions of PG are extremely rare and have not been previously reported on chronic leukemia patient.
CLINICAL REPORT: This report presents the first case of a 73 year-old man who had PG-like oral ulcerations which offered the possibility of an initial finding of chronic myeloid leukemia.
CONCLUSION: Clinicians should always take into consideration that PG in the oral mucosa is a recalcitrant ulcer and can precede the development of underlying clonal malignancy.

PMID: 26768815 [PubMed - indexed for MEDLINE]

16 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 2017/05/30

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.

16 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 2017/05/30

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.

Lessons from Retinoblastoma: Implications for Cancer, Development, Evolution, and Regenerative Medicine.

Trends Mol Med. 2016 Oct;22(10):863-876

Authors: Dyer MA

Abstract
Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology. Retinoblastoma has also emerged as a model for translational research for pediatric solid tumors, which is particularly important as personalized medicine expands in oncology. Research on retinoblastomas has been combined with the exploration of retinal development and retinal degeneration to advance a new model of cell type-specific disease susceptibility termed 'cellular pliancy'. The concept can even be extended to species-specific regeneration. This review discusses the remarkable path of retinoblastoma research and how it has shaped the most current efforts in basic, translational, and clinical research in oncology and beyond.

PMID: 27567287 [PubMed - indexed for MEDLINE]

[Anesthetic management of two patients with alkaptonuric ochronosis for total knee arthroplasty].

Rev Bras Anestesiol. 2017 May 20;:

Authors: Kozanhan B

Abstract
The current case report describes two cases of alkaptonuric ochronosis for anesthetic management. Alkaptonuria is a rare genetic orphan disease of tyrosine metabolism characterized by an accumulation of homogentisic acid in cartilage and connective tissues. Patients present most commonly for orthopedic joint surgery due to progressive arthropathy that can be misdiagnosed many a times. However respiratory, airway, cardiovascular and genitourinary systems complications can occur with age progressing. Restricted range of motion of cervical spine may lead to difficulty with airway management. In addition, degenerative changes and stiffness of lumbar spine due to ochronosis would make neuraxial blockade challenging. Although this inherited condition is extremely rare, anesthesiologists should be aware of its existence and prepare for management of potential challenging problems. This report highlights special care and precautions that need to be taken during anesthetic management.

PMID: 28535941 [PubMed - as supplied by publisher]

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Am J Hum Genet. 2017 01 05;100(1):75-90

Authors: Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, Carmichael J, Chitre M, Henderson RH, Hurst J, MacLaren RE, Murphy E, Paterson J, Rosser E, Thompson DA, Wakeling E, Ouwehand WH, Michaelides M, Moore AT, NIHR-BioResource Rare Diseases Consortium, Webster AR, Raymond FL

Abstract
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.

PMID: 28041643 [PubMed - indexed for MEDLINE]

The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States.

J Hum Genet. 2017 Feb;62(2):243-252

Authors: Reddy HM, Cho KA, Lek M, Estrella E, Valkanas E, Jones MD, Mitsuhashi S, Darras BT, Amato AA, Lidov HG, Brownstein CA, Margulies DM, Yu TW, Salih MA, Kunkel LM, MacArthur DG, Kang PB

Abstract
The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD) in the United States using whole-exome sequencing. Fifty-five families affected by LGMD were recruited using an institutionally approved protocol. Exome sequencing was performed on probands and selected parental samples. Pathogenic mutations and cosegregation patterns were confirmed by Sanger sequencing. Twenty-two families (40%) had novel and previously reported pathogenic mutations, primarily in LGMD genes, and also in genes for Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, congenital myopathy, myofibrillar myopathy, inclusion body myopathy and Pompe disease. One family was diagnosed via clinical testing. Dominant mutations were identified in COL6A1, COL6A3, FLNC, LMNA, RYR1, SMCHD1 and VCP, recessive mutations in ANO5, CAPN3, GAA, LAMA2, SGCA and SGCG, and X-linked mutations in DMD. A previously reported variant in DMD was confirmed to be benign. Exome sequencing is a powerful diagnostic tool for LGMD. Despite careful phenotypic screening, pathogenic mutations were found in other muscle disease genes, largely accounting for the increased sensitivity of exome sequencing. Our experience suggests that broad sequencing panels are useful for these analyses because of the phenotypic overlap of many neuromuscular conditions. The confirmation of a benign DMD variant illustrates the potential of exome sequencing to help determine pathogenicity.

PMID: 27708273 [PubMed - indexed for MEDLINE]

Epidemiological investigations on the potential transmissibility of a rare disease: the case of atypical scrapie in Great Britain.

Epidemiol Infect. 2016 Jul;144(10):2107-16

Authors: Ortiz-Peláez A, Arnold ME, Vidal-Diez A

Abstract
Multiple cases of atypical scrapie in the same holding and co-existence with classical scrapie have been reported in Great Britain. A two-stage simulation tool was developed by combining a sampling algorithm and a hierarchical Bayesian model to simulate the number of positive cases of atypical scrapie from: (i) random sampling and (ii) using the actual sampled population in Great Britain, being the output probability of detection of flocks with one and more cases. Cluster analysis was conducted to assess the level of geographical over- and under-sampling over the years. The probability of detecting at least two cases of atypical scrapie in the same holding is much lower in simulated random data than in simulated actual data for all scenarios. Sampling bias in the selection of sheep for testing led to multiple sampling from fewer but larger holdings, Scotland, and areas of Wales were under-sampled and the South-West and East of England oversampled. The pattern of atypical scrapie cases observed is unlikely to be explained by a multi-case event epidemiologically linked. The co-existence of classical and atypical scrapie is a rare event with 19 holdings detected in GB and does not suggest an epidemiological link between the two types of disease.

PMID: 26976340 [PubMed - indexed for MEDLINE]

Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy.

Proc Natl Acad Sci U S A. 2017 May 22;:

Authors: Vieira NM, Spinazzola JM, Alexander MS, Moreira YB, Kawahara G, Gibbs DE, Mead LC, Verjovski-Almeida S, Zatz M, Kunkel LM

Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these "escaper" dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases.

PMID: 28533404 [PubMed - as supplied by publisher]

Progress towards generation of human haematopoietic stem cells.

Nat Cell Biol. 2016 Nov;18(11):1111-1117

Authors: Wahlster L, Daley GQ

Abstract
De novo generation of haematopoietic stem cells from different human pluripotent stem cell sources remains a high priority for haematology and regenerative medicine. At present, efficient derivation of functional haematopoietic stem cells with the capability for definitive in vivo engraftment and multi-lineage potential remains challenging. Here, we discuss recent progress and strategies to overcome obstacles that have thwarted past efforts. In addition, we review promising advances in the generation of mature blood lineages and the potential of induced pluripotent stem cells.

PMID: 27723718 [PubMed - indexed for MEDLINE]

Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF).

Ann Rheum Dis. 2016 Jun;75(6):1051-6

Authors: Demirkaya E, Acikel C, Hashkes P, Gattorno M, Gul A, Ozdogan H, Turker T, Karadag O, Livneh A, Ben-Chetrit E, Ozen S, FMF Arthritis Vasculitis and Orphan disease Research in pediatric rheumatology (FAVOR)

Abstract
OBJECTIVE: To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice.
METHODS: Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set.
RESULTS: A total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3-5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group.
CONCLUSIONS: The initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF.

PMID: 26823530 [PubMed - indexed for MEDLINE]

Finding Rare, Disease-Associated Variants in Isolated Groups: Potential Advantages of Mennonite Populations.

Hum Biol. 2016 Apr;88(2):109-120

Authors: Lopes FL, Hou L, Boldt AB, Kassem L, Alves VM, Nardi AE, McMahon FJ

Abstract
Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses.

PMID: 28162000 [PubMed - indexed for MEDLINE]

Acute anterior wall myocardial infraction in asymptomatic severe aortic Coarctation in young adult - A rare case.

Indian Heart J. 2016 Jul-Aug;68(4):523-4

Authors: Singhal G, Pathak V

Abstract
Coarctation of Aorta is not rare in general population. Aortic Coarctation represents about 5-8% of all congenital cardiac diseases, and it is commonly associated with bicuspid aortic valve. Coarctation of Aorta is typically a disease of childhood and early adulthood, reducing life expectancy in patients, who have not undergone correction. Many case reports of Coarctation of Aorta patients presenting with anterior wall myocardial infraction have been published in various journals, but to the best of our knowledge, no case of Coarctation of Aorta with acute anterior wall myocardial in 30-year-old male is reported till date. We are presenting a rare case of anterior wall myocardial infraction in young male with asymptomatic Coarctation of Aorta.

PMID: 27543476 [PubMed - indexed for MEDLINE]

Pre-referral GP consultations in patients subsequently diagnosed with rarer cancers: a study of patient-reported data.

Br J Gen Pract. 2016 Mar;66(644):e171-81

Authors: Mendonca SC, Abel GA, Lyratzopoulos G

Abstract
BACKGROUND: Some patients with cancer experience multiple pre-diagnostic consultations in primary care, leading to longer time intervals to specialist investigations and diagnosis. Patients with rarer cancers are thought to be at higher risk of such events, but concrete evidence of this is lacking.
AIM: To examine the frequency and predictors of repeat consultations with GPs in patients with rarer cancers.
DESIGN AND SETTING: Patient-reported data on pre-referral consultations from three English national surveys of patients with cancer (2010, 2013, and 2014), pooled to maximise the sample size of rarer cancers.
METHOD: The authors examined the frequency and crude and adjusted odds ratios for ≥3 (versus 1-2) pre-referral consultations by age, sex, ethnicity, level of deprivation, and cancer diagnosis (38 diagnosis groups, including 12 rarer cancers without prior relevant evidence).
RESULTS: Among 7838 patients with 12 rarer cancers, crude proportions of patients with ≥3 pre-referral consultations ranged from >30.0% to 60.0% for patients with small intestine, bone sarcoma, liver, gallbladder, cancer of unknown primary, soft-tissue sarcoma, and ureteric cancer. The range was 15.0-30.0% for patients with oropharyngeal, anal, parotid, penile, and oral cancer. The overall proportion of responders with any cancer who had ≥3 consultations was 23.4%. Multivariable logistic regression indicated concordant patterns, with strong evidence for variation between rarer cancers (P <0.001).
CONCLUSION: Patients with rarer cancers experience pre-referral consultations at frequencies suggestive of middle-to-high diagnostic difficulty. The findings can guide the development of new diagnostic interventions and 'safety-netting' approaches for symptomatic presentations encountered in patients with rarer cancers.

PMID: 26917657 [PubMed - indexed for MEDLINE]