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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/15

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/15

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/14

PubMed comprises more than 24 million 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.

RareVariantVis: new tool for visualization of causative variants in rare monogenic disorders using whole genome sequencing data.

Bioinformatics. 2016 Jun 10;

Authors: Stokowy T, Garbulowski M, Fiskerstrand T, Holdhus R, Labun K, Sztromwasser P, Gilissen C, Hoischen A, Houge G, Petersen K, Jonassen I, Steen VM

Abstract
MOTIVATION: The search for causative genetic variants in rare diseases of presumed monogenic inheritance has been boosted by the implementation of whole exome (WES) and whole genome (WGS) sequencing. In many cases, WGS seems to be superior to WES, but the analysis and visualization of the vast amounts of data is demanding.
RESULTS: To aid this challenge, we have developed a new tool - RareVariantVis - for analysis of genome sequence data (including non-coding regions) for both germ line and somatic variants. It visualizes variants along their respective chromosomes, providing information about exact chromosomal position, zygosity and frequency, with point-and-click information regarding dbSNP IDs, gene association and variant inheritance. Rare variants as well as de novo variants can be flagged in different colors. We show the performance of the RareVariantVis tool in the Genome in a Bottle WGS data set.
AVAILABILITY: https://www.bioconductor.org/packages/3.3/bioc/html/RareVariantVis.html CONTACT: tomasz.stokowy@k2.uib.no SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID: 27288501 [PubMed - as supplied by publisher]

A giant adrenal myelolipoma in a beta-thalassemia major patient: Does ineffective erythropoiesis play a role?

Am J Hematol. 2016 Jun 10;

Authors: Motta I, Boiocchi L, Delbini P, Migone De Amicis M, Cassinerio E, Dondossola D, Rossi G, Cappellini MD

PMID: 27288248 [PubMed - as supplied by publisher]

Identification of genetic variants in pharmacokinetic genes associated with Ewing Sarcoma treatment outcome.

Ann Oncol. 2016 Jun 10;

Authors: Ruiz-Pinto S, Pita G, Patiño-García A, García-Miguel P, Alonso J, Pérez-Martínez A, Sastre A, Gómez-Mariano G, Lissat A, Scotlandi K, Serra M, Ladenstein R, Lapouble E, Pierron G, Kontny U, Picci P, Kovar H, Delattre O, González-Neira A

Abstract
BACKGROUND: Despite the effectiveness of current treatment protocols for Ewing sarcoma (ES), many patients still experience relapse, and survival following recurrence is less than 15%. We aimed to identify genetic variants that predict treatment outcome in children diagnosed with ES.
PATIENTS AND METHODS: We carried out a pharmacogenetic study of 384 single nucleotide polymorphisms (SNPs) in 24 key transport or metabolism genes relevant to drugs used to treat in pediatric patients (<30 years) with histologically confirmed ES. We studied the association of genotypes with tumor response and overall survival (OS) in a discovery cohort of 106 Spanish children, with replication in a second cohort of 389 pediatric patients from across Europe.
RESULTS: We identified associations with OS (P<0.05) for three SNPs in the Spanish cohort that were replicated in the European cohort. The strongest association observed was with rs7190447, located in the ATP-binding cassette sub-family C member 6 (ABCC6) gene (discovery: HR=14.30, 95%CI=1.53-134, P=0.020; replication: HR=9.28, 95%CI=2.20-39.2, P=0.0024) and its correlated SNP rs7192303, which was predicted to have a plausible regulatory function. We also replicated associations with rs4148737 in the ATP-binding cassette sub-family B member 1 (ABCB1) gene (discovery: HR=2.96, 95%CI=1.08-8.10, P=0.034; replication: HR=1.60, 95%CI=1.05-2.44, P=0.029), which we have previously found to be associated with poorer OS in pediatric osteosarcoma patients, and rs11188147 in cytochrome P450 family 2 subfamily C member 8 gene (CYP2C8) (discovery : HR=2.49, 95%CI=1.06-5.87, P=0.037; replication: HR=1.77, 95%CI=1.06-2.96, P=0.030), an enzyme involved in the oxidative metabolism of the ES chemotherapeutic agents cyclophosphamide and ifosfamide. None of the associations with tumor response were replicated.
CONCLUSION: Using an integrated pathway-based approach we identified polymorphisms in ABCC6, ABCB1 and CYP2C8 associated with OS. These associations were replicated in a large independent cohort, highlighting the importance of pharmacokinetic genes as prognostic markers in ES.

PMID: 27287205 [PubMed - as supplied by publisher]

The Story of Angioedema: from Quincke to Bradykinin.

Clin Rev Allergy Immunol. 2016 Jun 10;

Authors: Reshef A, Kidon M, Leibovich I

Abstract
The term "swelling" has been used in the old scriptures to illustrate a change of normal figure and, as such, an expression of illness. It should be noted that in ancient times, human diseases were very often regarded a punishment from God. Hence, it is not surprising that one of the oldest tests for infidelity involved swelling as an inflicted punishment. The great Greek physician Hippocrates (377-460 BC), considered one of the most outstanding figures in the history of medicine and "Father of the Western Medicine," already used the term oídēma to describe swelling of organs. It took many centuries later until the first description of angioedema as a distinct medical entity was minted by Quinke in 1882. The historical progression in angioedema research has been characterized by intermittent "leaps" in interest and scientific achievements. As an example, it took 75 years from the accurate description of hereditary angioedema (HAE) by Osler (1888), until a group of researchers headed by Donaldson (1963) disclosed the central role of C1 inhibitor in angioedema pathophysiology. What followed was a result of a collective effort by many researchers and scientific groups who were able to elucidate the intricate connections between the implicated biochemical pathways. Still, scientific progress was hardly translated into effective therapy, and another 45 years had to elapse until the renewed interest in HAE was boosted by studies on the efficacy and safety of novel therapies about 10 years ago. In the twenty-first century, HAE ceased to be an "orphan disease" and its future is far more optimistic. It is better managed now by specialized angioedema centers, harmonized clinical guidelines, educational programs, laboratory services, and continued basic and clinical research. Patient associations worldwide are offering support and guidance, and governments and healthcare systems are gradually addressing patient and family needs.

PMID: 27287037 [PubMed - as supplied by publisher]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/11

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/10

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/09

PubMed comprises more than 24 million 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.

Primary Immune Deficiency Treatment Consortium (PIDTC) update.

J Allergy Clin Immunol. 2016 Apr 22;

Authors: Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E, workshop participants

Abstract
The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PIDs), including severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PIDs in multicenter longitudinal retrospective, prospective, and cross-sectional studies. Since 2009, participating centers have enrolled more than 800 subjects on PIDTC protocols for SCID, and enrollment in the studies on WAS and CGD is underway. Four pilot projects have been funded, and 12 junior investigators have received fellowship awards. Important publications of the consortium describe the outcomes of hematopoietic cell transplantation for SCID during 2000-2009, diagnostic criteria for SCID, and the pilot project of newborn screening for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups, and international colleagues. Funded by the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, the PIDTC has recently received renewal for another 5 years. Here we review accomplishments of the group, projects underway, highlights of recent workshops, and challenges for the future.

PMID: 27262745 [PubMed - as supplied by publisher]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/05

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/04

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/03

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/02

PubMed comprises more than 24 million 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.

Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis.

JAMA Neurol. 2016 May 31;

Authors: Fogh I, Lin K, Tiloca C, Rooney J, Gellera C, Diekstra FP, Ratti A, Shatunov A, van Es MA, Proitsi P, Jones A, Sproviero W, Chiò A, McLaughlin RL, Sorarù G, Corrado L, Stahl D, Del Bo R, Cereda C, Castellotti B, Glass JD, Newhouse S, Dobson R, Smith BN, Topp S, van Rheenen W, Meininger V, Melki J, Morrison KE, Shaw PJ, Leigh PN, Andersen PM, Comi GP, Ticozzi N, Mazzini L, D'Alfonso S, Traynor BJ, Van Damme P, Robberecht W, Brown RH, Landers JE, Hardiman O, Lewis CM, van den Berg LH, Shaw CE, Veldink JH, Silani V, Al-Chalabi A, Powell J

Abstract
Importance: Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset.
Objective: To identify gene variants influencing survival in ALS.
Design, Setting, and Participants: This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015.
Main Outcomes and Measures: Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed by meta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis.
Results: Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 × 10-9) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 × 10-8). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 × 10-9), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 × 10-8), corresponding to a 4-month reduction in survival compared with TT carriers.
Conclusions and Relevance: This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.

PMID: 27244217 [PubMed - as supplied by publisher]

How can clinical ethics guide the management of comorbidities in the child with Rett syndrome?

J Paediatr Child Health. 2016 May 31;

Authors: Downs J, Forbes D, Johnson M, Leonard H

Abstract
Rett syndrome is a rare disorder caused by a mutation in the MECP2 gene. Those affected generally have severe functional impairments, and medical comorbidities such as scoliosis and poor growth are common. There is a paucity of information on the natural history of many rare disorders and an even greater deficit of evidence to guide best practice. The population-based and longitudinal Australian Rett Syndrome Database established in 1993 has supported investigations of the natural history of Rett syndrome and effectiveness of treatments. This paper reviews the disorder Rett syndrome and evidence for the management of scoliosis and poor growth within a clinical ethics framework. Compared with conservative management, we have shown that spinal fusion is associated with reduced mortality and better respiratory health. We have also shown that gastrostomy insertion is associated with subsequent weight gain. Family counselling for both procedures necessarily must include family perspectives and careful clinical attention to their needs and wishes. Vignettes describing family decision-making and experiences are presented to illustrate the principals of beneficence and autonomy in determining the best interests of the child and family. A blend of evidence-based practice with a strong clinical ethics framework has capacity to build existing strengths in families and reduce the negative impacts of disability and in so doing, optimise the health and wellbeing of those with Rett syndrome.

PMID: 27243819 [PubMed - as supplied by publisher]

Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit.

CMAJ. 2016 May 30;

Authors: Daoud H, Luco SM, Li R, Bareke E, Beaulieu C, Jarinova O, Carson N, Nikkel SM, Graham GE, Richer J, Armour C, Bulman DE, Chakraborty P, Geraghty M, Lines MA, Lacaze-Masmonteil T, Majewski J, Boycott KM, Dyment DA

Abstract
BACKGROUND: Rare diseases often present in the first days and weeks of life and may require complex management in the setting of a neonatal intensive care unit (NICU). Exhaustive consultations and traditional genetic or metabolic investigations are costly and often fail to arrive at a final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed the feasibility of next-generation sequencing as a tool to improve the diagnosis of rare diseases in newborns in the NICU.
METHODS: We retrospectively identified and prospectively recruited newborns and infants admitted to the NICU of the Children's Hospital of Eastern Ontario and the Ottawa Hospital, General Campus, who had been referred to the medical genetics or metabolics inpatient consult service and had features suggesting an underlying genetic or metabolic condition. DNA from the newborns and parents was enriched for a panel of clinically relevant genes and sequenced on a MiSeq sequencing platform (Illumina Inc.). The data were interpreted with a standard informatics pipeline and reported to care providers, who assessed the importance of genotype-phenotype correlations.
RESULTS: Of 20 newborns studied, 8 received a diagnosis on the basis of next-generation sequencing (diagnostic rate 40%). The diagnoses were renal tubular dysgenesis, SCN1A-related encephalopathy syndrome, myotubular myopathy, FTO deficiency syndrome, cranioectodermal dysplasia, congenital myasthenic syndrome, autosomal dominant intellectual disability syndrome type 7 and Denys-Drash syndrome.
INTERPRETATION: This pilot study highlighted the potential of next-generation sequencing to deliver molecular diagnoses rapidly with a high success rate. With broader use, this approach has the potential to alter health care delivery in the NICU.

PMID: 27241786 [PubMed - as supplied by publisher]

Genotyping of relapsing polychondritis identified novel susceptibility HLA alleles and distinct genetic characteristics from other rheumatic diseases.

Rheumatology (Oxford). 2016 May 30;

Authors: Terao C, Yoshifuji H, Yamano Y, Kojima H, Yurugi K, Miura Y, Maekawa T, Handa H, Ohmura K, Saji H, Mimori T, Matsuda F

Abstract
OBJECTIVE: To uncover the genetic background of relapsing polychondritis (RPC), a rare autoimmune disease with unknown mechanisms characterized by systemic inflammation of the cartilage, to deepen our understanding of the pathophysiology of RPC and show its distinct genetic characteristics from other rheumatic diseases.
METHODS: A total of 102 patients with RPC and 1000 healthy subjects were recruited for a two-staged genetic association study and genotyped for six HLA classical loci. Haplotype association tests were also performed. The associations of amino acid (AA) residues and positions with susceptibility to RPC were analysed. Frequencies of representative susceptibility HLA alleles to other rheumatic diseases in RPC were also analysed.
RESULTS: HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, which are in linkage disequilibrium with each other, were associated with RPC (P = 1.9 × 10(-6), 1.4 × 10(-5) and 0.00024, respectively). AA residue at position 57 in HLA-DQB1, the most significant position in type I diabetes mellitus, showed the strongest association among AA residues. HLA-DR4, a known susceptibility allele in Germans, showed a trend of susceptibility association without significance (P = 0.067). No associations were observed between the three alleles and clinical phenotypes. Representative susceptibility HLA alleles to RA, SLE, Behçet disease and Takayasu arteritis did not show enrichment in RPC in spite of sufficient statistical power.
CONCLUSIONS: HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, in linkage disequilibrium with each other, are associated with susceptibility to RPC Importance of HLA-class II loci in RPC susceptibility is suggested. RPC is considered a genetically distinct disease from other rheumatic diseases.

PMID: 27241705 [PubMed - as supplied by publisher]

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations.

Curr Osteoporos Rep. 2016 May 30;

Authors: Canalis E, Zanotti S

Abstract
Notch plays an important function in skeletal homeostasis, osteoblastogenesis, and osteoclastogenesis. Hajdu-Cheney syndrome (HCS) is a rare disease associated with mutations in NOTCH2 leading to the translation of a truncated NOTCH2 stable protein. As a consequence, a gain-of-NOTCH2 function is manifested. HCS is inherited as an autosomal dominant disease although sporadic cases exist. HCS is characterized by craniofacial developmental defects, including platybasia and wormian bones, osteoporosis with fractures, and acro-osteolysis. Subjects may suffer severe neurological complications, and HCS presents with cardiovascular defects and polycystic kidneys. An experimental mouse model harboring a HCSNotch2 mutation exhibits osteopenia secondary to enhanced bone resorption suggesting this as a possible mechanism for the skeletal disease. If the same mechanisms were operational in humans, anti-resorptive therapy could correct the bone loss, but not necessarily the acro-osteolysis. In conclusion, HCS is a devastating disease associated with a gain-of-NOTCH2 function resulting in diverse clinical manifestations.

PMID: 27241678 [PubMed - as supplied by publisher]