Bullous aplasia cutis congenita: A rare presentation of a rare disease.

Dermatol Online J. 2020 Feb 15;26(2):

Authors: Watchmaker L, Watchmaker J

Abstract
Aplasia cutis congenita (ACC) is a congenital disorder characterized by localized or generalized absence of skin. Bullous aplasia cutis congenita (BACC) is a rare clinical subtype that has few documented reports in the literature. Herein, we present a new case of BACC in which the bulla was unruptured at birth.

PMID: 32239901 [PubMed - indexed for MEDLINE]

AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature.

Sci Transl Med. 2020 May 20;12(544):

Authors: Birgmeier J, Haeussler M, Deisseroth CA, Steinberg EH, Jagadeesh KA, Ratner AJ, Guturu H, Wenger AM, Diekhans ME, Stenson PD, Cooper DN, Ré C, Beggs AH, Bernstein JA, Bejerano G

Abstract
The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication(s) supporting a single gene that best explains a patient's disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts and downloads and further parses hundreds of thousands of full-text articles in search of information supporting the causality and associated phenotypes of most published genetic variants. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient's given set of phenotypes. Diagnosis of singleton patients (without relatives' exomes) is the most time-consuming scenario, and AMELIE ranked the causative gene at the very top for 66% of 215 diagnosed singleton Mendelian patients from the Deciphering Developmental Disorders project. Evaluating only the top 11 AMELIE-scored genes of 127 (median) candidate genes per patient resulted in a rapid diagnosis in more than 90% of cases. AMELIE-based evaluation of all cases was 3 to 19 times more efficient than hand-curated database-based approaches. We replicated these results on a retrospective cohort of clinical cases from Stanford Children's Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface, and code is available at AMELIE.stanford.edu.

PMID: 32434849 [PubMed - in process]

Will the US$5 million onasemnogene abeparvosec treatment for spinal muscular atrophy represent 'value for money' for the NHS? A rapid inquiry into suggestions that it may be cost-effective.

Expert Opin Biol Ther. 2020 May 20;:

Authors: Connock M, Andronis L, Auguste P, Dussart C, Armoiry X

Abstract
Objectives Nusinersen (Spinraza®, Biogen) and onasemnogene abeparvosec (Zolgensma®, Novartis) are novel gene-based therapies for the orphan disease Spinal Muscular Atrophy. Onasemnogene abeparvosec has been allocated an acquisition cost of up to US$5 million per patient. We undertook a rapid inquiry to evaluate if onasemnogene abeparvosec is likely to be cost effective for the UK NHS. Methods We used publicly available cost effectiveness data and recommended methodology to perform cost utility evaluation of onasemnogene abeparvosec versus best supportive care and nusinersen. Results Our evaluations highlight wide variations in cost and benefit estimates of nusinersen and indicate that onasemnogene abeparvosec is unlikely to represent value for money according to current standards of reimbursement. Results are discussed in the context of reimbursement decisions for orphan diseases. Conclusion Commonly implemented commercial confidentiality practices combined with uncertain data obscure scrutiny and justification of past and present reimbursement decisions for orphan drugs. Future cutting edge expensive therapies will be numerous, they will entail very substantial economic strains. We conclude that there is an urgent and increasing need for the development of improved procedures that can lead to equitable, consistent and transparent decision making.

PMID: 32434404 [PubMed - as supplied by publisher]

Spotlight on rare diseases.

Lancet Diabetes Endocrinol. 2019 02;7(2):75

Authors: The Lancet Diabetes Endocrinology

PMID: 30683214 [PubMed - indexed for MEDLINE]

A multinational, multi-tumour basket study in very rare cancer types: The European Organization for Research and Treatment of Cancer phase II 90101 'CREATE' trial.

Eur J Cancer. 2019 03;109:192-195

Authors: Péron J, Marreaud S, Staelens D, Raveloarivahy T, Nzokirantevye A, Flament J, Steuve J, Lia M, Collette L, Schöffski P

PMID: 30655100 [PubMed - indexed for MEDLINE]

12 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 2020/05/21

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.

12 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 2020/05/21

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.

A Rare Manifestation of a Rare Disease: Mantle Cell Lymphoma Presenting With Aseptic Meningitis.

J Investig Med High Impact Case Rep. 2019 Jan-Dec;7:2324709619858643

Authors: Umyarova E, Adapa S, Naramala S, Gayam V, Aeddula NR, Konala VM

Abstract
Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma characterized by clonal proliferation of follicular mantle zone B lymphocytes. It is caused by abnormal chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. This leads to activation of anti-apoptotic pathways and abnormal proliferation of MCL cells. Patients can present with an indolent course or a fulminant disease with short overall survival. The disease frequently involves extranodal organs, but rarely manifests with neurological symptoms. We report a rare case of aberrant CD5-negative MCL presenting with aseptic meningitis.

PMID: 31234647 [PubMed - indexed for MEDLINE]

Coincidence of Andersen-Tawil syndrome and Marfan syndrome: A case report.

Ann Noninvasive Electrocardiol. 2019 05;24(3):e12624

Authors: Krych M, Ponińska J, Bilińska ZT, Płoski R, Biernacka EK

Abstract
We report on a 44-year-old woman with coincidence of two genetic disorders: Andersen-Tawil syndrome and Marfan syndrome. In both, life-threatening arrhythmias could occur. A 44-year-old woman presented acute ascending aortic dissection with aortic arch involvement and chronic thoracic descending and abdominal aortic dissection. Clinical and genetic examination confirmed Marfan syndrome (MFS) diagnosis. Due to repolarization disorder in ECG and premature ventricular contractions in Holter ECG, the sequencing data were analyzed again and mutation in KCNJ2 gene was identified. The case showed that coincidence of Andersen-Tawil syndrome (ATS) and MFS did not provoke life-threatening arrhythmias. Complication was rather caused by expression of FBN1 mutation.

PMID: 30672637 [PubMed - indexed for MEDLINE]

Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia.

Ann Noninvasive Electrocardiol. 2019 05;24(3):e12623

Authors: Dharmawan T, Nakajima T, Ohno S, Iizuka T, Tamura S, Kaneko Y, Horie M, Kurabayashi M

Abstract
BACKGROUND: RYR2, encoding cardiac ryanodine receptor, is the major responsible gene for catecholaminergic polymorphic ventricular tachycardia (CPVT). Meanwhile, KCNJ2, encoding inward-rectifier potassium channel (IK1 ), can be the responsible gene for atypical CPVT. We recently encountered a family with CPVT and sought to identify a responsible gene variant.
METHODS: A targeted panel sequencing (TPS) was employed in the proband. Copy number variation (CNV) in RYR2 was identified by focusing on read numbers in the TPS and long-range PCR. Cascade screening was conducted by a Sanger method and long-range PCR. KCNJ2 wild-type (WT) or an identified variant was expressed in COS-1 cells, and whole-cell currents (IK1 ) were recorded using patch-clamp techniques.
RESULTS: A 40-year-old female experienced cardiopulmonary arrest while cycling. Her ECG showed sinus bradycardia with prominent U-waves (≥0.2 mV). She had left ventricular hypertrabeculation at apex. Exercise induced frequent polymorphic ventricular arrhythmias. Her sister died suddenly at age 35 while bouldering. Her father and paternal aunt, with prominent U-waves, received permanent pacemaker due to sinus node dysfunction. The initial TPS and cascade screening identified a KCNJ2 E118D variant in all three symptomatic patients. However, after focusing on read numbers, we identified a novel exon3 deletion of RYR2 (RYR2-exon3 deletion) in all of them. Functional analysis revealed that KCNJ2 E118D generated IK1 indistinguishable from KCNJ2 WT, even in the presence of catecholaminergic stimulation.
CONCLUSIONS: Focusing on the read numbers in the TPS enabled us to identify a novel CNV, RYR2-exon3 deletion, which was associated with phenotypic features of this family.

PMID: 30615235 [PubMed - indexed for MEDLINE]

11 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 2020/05/19

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.

Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors.

Eur J Cancer. 2019 03;110:120-126

Authors: Ferrari A, Brecht IB, Gatta G, Schneider DT, Orbach D, Cecchetto G, Godzinski J, Reguerre Y, Bien E, Stachowicz-Stencel T, Ost M, Magni C, Kearns P, Vassal G, Massimino M, Biondi A, Bisogno G, Trama A

Abstract
Although all tumours are rare in childhood, there are some particularly rare paediatric cancers which have not benefited from advances made by the international paediatric oncology network. To establish a shared definition and produce a list of these entities, the European Union Joint Action on Rare Cancers (JARC) promoted a consensus effort. The definition was based on the incidence rates estimated using the information network on rare cancers (RARECAREnet) database, pooling data from 94 population-based cancer registries and 27 countries. The RARECAREnet list of cancers was used to estimate the incidence rates. This list groups cancers by combining the International Classification of Diseases for Oncology, third edition, morphology and topography codes. According to the consensus, very rare paediatric cancers were identified as those with an annual incidence <2/1000000 and corresponded to 11% of all cancers in patients aged 0-14 years. Two subgroups were identified: tumour types typical of childhood (i.e. hepatoblastoma, pleuropulmonary blastoma, pancreatoblastoma) and those typical of adult age (i.e. carcinomas, melanoma). The threshold of 2/1000000 could also be adopted in populations aged 0-19 years: in this case, three tumour types had an incidence rate which was >2/1000000 (i.e. thyroid and testicular cancers and skin melanoma), but the consensus experts considered them as 'very rare' according to their clinical needs (e.g. shortage of knowledge and clinical expertise as the other rare paediatric cancers). The JARC consensus produced a definition and a list of very rare paediatric cancers which may represent a starting point for prioritising research on these tumours, based on data and patients' clinical needs.

PMID: 30785015 [PubMed - indexed for MEDLINE]

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 2020/05/15

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.

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 2020/05/15

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.

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 2020/05/14

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.

Congenital Heart Defects Due to TAF1 Missense Variants.

Circ Genom Precis Med. 2020 May 12;:

Authors: Morton SU, Agarwal R, Madden JA, Genetti CA, Brownstein CA, López-Giráldez F, Choi J, Seidman CE, Seidman JG, Lyon GJ, Agrawal PB

PMID: 32396742 [PubMed - as supplied by publisher]

A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care.

JIMD Rep. 2020 May;53(1):71-79

Authors: Rudebeck M, Scott C, Sireau N, Ranganath L

Abstract
Background: Alkaptonuria (AKU) is an ultrarare and multifaceted disease characterized by the absence of functional homogentisate 1,2-dioxygenase activity, the enzyme responsible for breakdown of homogentisic acid-a tyrosine-degradation product. The presymptomatic phase of the disease makes diagnosis difficult, with many patients unidentified or diagnosed late in life.
Objective: To date, no study has analyzed the perceived impact of different symptoms or the experiences of individuals through the patient journey in the context of AKU. This study aimed to examine patients' perceptions of AKU symptoms and their impact on quality of life as well as patients' experiences of being diagnosed and living with the disease.
Methods: Data for this study were collected using a quantitative self-report questionnaire administered online to people with AKU.
Results: Data from 45 participants indicate that symptoms with the highest impact for patients are those related to pain and ruptures, disability and inability to perform normal routines, emotional/mental health issues, and heart complications. Findings also revealed significant delays in contact with healthcare services and time to diagnosis. Furthermore, patients reported difficulty in receiving information about AKU, treatment and care, and long-term disease management support.
Conclusions: Time to diagnosis and care of AKU is significantly delayed. Symptoms of AKU with the highest impact on quality of life for patients are those related to pain and disability and the inability to perform normal routines. Bridging any gaps between patients with AKU and healthcare professionals through education could help improve patients' experiences with AKU through the patient journey.

PMID: 32395411 [PubMed]

TAILORx: Questions Answered, Lessons Learned, and Remaining Knowledge Gaps.

J Clin Oncol. 2019 07 20;37(21):1841-1842

Authors: Sparano JA, Gray R

PMID: 31173552 [PubMed - indexed for MEDLINE]

8 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 2020/05/12

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.

8 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 2020/05/12

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.