Mesenteriales, zystisches Lymphangiom beim Erwachsenen – eine Rarität als Zufallsbefund.

Praxis (Bern 1994). 2016 Sep;105(20):1213-1216

Authors: Nagy A, Fretz C, Bergelt S, Semadeni GM, Meyenberger C

PMID: 27705195 [PubMed - indexed for MEDLINE]

Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome.

Genome Res. 2017 Jun 19;:

Authors: Evrony GD, Cordero DR, Shen J, Partlow JN, Yu TW, Rodin RE, Hill RS, Coulter ME, Lam AN, Jayaraman D, Gerrelli D, Diaz DG, Santos C, Morrison V, Galli A, Tschulena U, Wiemann S, Martel MJ, Spooner B, Ryu SC, Elhosary PC, Richardson JM, Tierney D, Robinson CA, Chibbar R, Diudea D, Folkerth R, Wiebe S, Barkovich AJ, Mochida GH, Irvine J, Lemire EG, Blakley P, Walsh CA

Abstract
While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS). MMS is an autosomal recessive condition described thus far in only a single First Nations population and causes intrauterine growth restriction, severe microcephaly, craniofacial anomalies, skeletal dysplasia, and neonatal lethality. Linkage analysis of affected families, including a very large pedigree, identified a single locus on Chromosome 21 linked to the disease (LOD > 9). Comprehensive genome sequencing did not reveal any pathogenic coding or canonical splicing mutations within the linkage region but identified several nonconserved noncoding variants. RNA-seq analysis detected aberrant splicing in DONSON due to one of these noncoding variants, showing a causative role for DONSON disruption in MMS. We show that DONSON is expressed in progenitor cells of embryonic human brain and other proliferating tissues, is co-expressed with components of the DNA replication machinery, and that Donson is essential for early embryonic development in mice as well, suggesting an essential conserved role for DONSON in the cell cycle. Our results demonstrate the utility of integrating transcriptomics into the study of human genetic disease when DNA sequencing alone is not sufficient to reveal the underlying pathogenic mutation.

PMID: 28630177 [PubMed - as supplied by publisher]

A rare adult renal neuroblastoma better imaged by (18)F-FDG than by (68)Ga-dotanoc in the PET/CT scan.

Hell J Nucl Med. 2017 Jan-Apr;20(1):100-101

Authors: Jain TK, Singh SK, Sood A, Ashwathanarayama AG, Basher RK, Shukla J, Mittal BR

Abstract
Primary renal neuroblastoma is an uncommon tumor in children and extremely rare in adults. We present a case of a middle aged female having a large retroperitoneal mass involving the right kidney with features of neuroblastoma on pre-operative histopathology. Whole-body fluorine-18-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET/CT) and (68)Ga-dotanoc PET/CT scans performed for staging and therapeutic potential revealed a tracer avid mass replacing the right kidney and also pelvic lymph nodes. The (18)F-FDG PET/CT scan showed better both the primary lesion and the metastases in the pelvic lymph nodes than the (68)Ga-dotanoc scan supporting diagnosis and treatment planning.

PMID: 28315919 [PubMed - indexed for MEDLINE]

'You should at least ask'. The expectations, hopes and fears of rare disease patients on large-scale data and biomaterial sharing for genomics research.

Eur J Hum Genet. 2016 Oct;24(10):1403-8

Authors: McCormack P, Kole A, Gainotti S, Mascalzoni D, Molster C, Lochmüller H, Woods S

Abstract
Within the myriad articles about participants' opinions of genomics research, the views of a distinct group - people with a rare disease (RD) - are unknown. It is important to understand if their opinions differ from the general public by dint of having a rare disease and vulnerabilities inherent in this. Here we document RD patients' attitudes to participation in genomics research, particularly around large-scale, international data and biosample sharing. This work is unique in exploring the views of people with a range of rare disorders from many different countries. The authors work within an international, multidisciplinary consortium, RD-Connect, which has developed an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for RD research. Focus groups were conducted with 52 RD patients from 16 countries. Using a scenario-based approach, participants were encouraged to raise topics relevant to their own experiences, rather than these being determined by the researcher. Issues include wide data sharing, and consent for new uses of historic samples and for children. Focus group members are positively disposed towards research and towards allowing data and biosamples to be shared internationally. Expressions of trust and attitudes to risk are often affected by the nature of the RD which they have experience of, as well as regulatory and cultural practices in their home country. Participants are concerned about data security and misuse. There is an acute recognition of the vulnerability inherent in having a RD and the possibility that open knowledge of this could lead to discrimination.

PMID: 27049302 [PubMed - indexed for MEDLINE]

10 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 2017/06/16

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.

Limits of Evidence Based Medicine for rare diseases: The case of Budd-Chiari syndrome.

Dig Liver Dis. 2016 Jun;48(6):689

Authors: Mancuso A

PMID: 27005858 [PubMed - indexed for MEDLINE]

[Bowel-associated dermatosis-arthritis syndrome during ulcerative colitis: A rare extra-intestinal sign of inflammatory bowel disease].

Ann Dermatol Venereol. 2016 May;143(5):377-81

Authors: Aounallah A, Zerriaa S, Ksiaa M, Jaziri H, Boussofara L, Ghariani N, Mokni S, Saidi W, Sriha B, Belajouza C, Denguezli M, Nouira R

Abstract
INTRODUCTION: Bowel-associated dermatosis-arthritis syndrome (BADAS) is characterized by combined pustular skin eruption and arthralgia. It may be associated with inflammatory bowel disease or bowel bypass surgery. We report a case of BADAS in a patient with ulcerative colitis.
CASE REPORT: A 39-year-old woman was being treated for a severe flare-up of ulcerative colitis present over the preceding 2 months and treated with prednisone, azathioprine and cyclosporine. She was also presenting a cutaneous eruption and arthralgia that had begun three days earlier. Dermatological examination revealed profuse vesicular and pustular lesions. Biopsy specimens showed mature neutrophilic infiltrate within the dermis. A diagnosis of BADAS was made and the same treatment was maintained. Systemic symptoms were resolved but the vesicular lesions were superseded by hypertrophic scars.
DISCUSSION: Bowel-associated dermatosis-arthritis syndrome consists of a vesiculopustular eruption associated with arthralgia and/or arthritis and fever, as was the case in our patient. The histological picture is characterized by abundant neutrophilic infiltrate in the superficial dermis. The clinical and histological features and the course of BADAS allow this entity to be classified within the spectrum of neutrophilic dermatoses. Treatment chiefly involves systemic corticosteroids.

PMID: 26988382 [PubMed - indexed for MEDLINE]

Primary malignant melanoma of the cervix: a rare disease.

BMJ Case Rep. 2017 Apr 21;2017:

Authors: Julião I, Carvalho SD, Patricio V, Raimundo A

Abstract
Malignant melanoma (MM) arising primarily in the cervix is exceedingly rare and has a poor prognosis. We report the case of a primary MM of the cervix in a 64-year-old woman with vaginal bleeding. She presented with a cervical amelanotic lesion which on biopsy rendered the diagnosis of MM. The patient was staged as International Federation of Gynecology and Obstetrics IIB and underwent Wertheim-Meigshysterectomy followed by brachytherapy. One year later, she was diagnosed with a large pelvic relapse for which surgery was performed. She then presented with a vaginal relapse and an isolated hepatic lesion, both of which were proposed for surgery. The diagnosis of MM of the cervix is a clinical and pathological challenge due to its rarity and overlapping features. Cytology cannot accurately diagnose it. Moreover, amelanotic MMs must be distinguished from other poorly differentiated carcinomas by diagnosis that ultimately relies on immunohistochemical staining. Radical surgery is the only treatment showing predictive benefit.

PMID: 28432169 [PubMed - indexed for MEDLINE]

Help Desk Answers: Do corticosteroids relieve Bell's palsy?

J Fam Pract. 2016 Mar;65(3):E1-2

Authors: Soch K, Purtle D, Ara M, Dabbs K

Abstract
Yes, but not severe disease. Corticosteroids likely improve facial motor function in adults with mild to moderate Bell's palsy. Corticosteroids are probably ineffective in treating cosmetically disabling or severe disease.

PMID: 27158696 [PubMed - indexed for MEDLINE]

Pott Puffy Tumor in Children: A Rare Emergency Clinical Entity.

J Craniofac Surg. 2016 May;27(3):e313-6

Authors: Palabiyik FB, Yazici Z, Cetin B, Celebi S, Hacimustafaoglu M

Abstract
OBJECTIVES: Pott puffy tumor (PPT) is defined as soft tissue swelling of the forehead due to subperiosteal edema, accumulation of pus, or granulation tissue. It is associated with osteomyelitis of frontal bone secondary to frontal sinusitis. Pott puffy tumor can be complicated by preseptal and orbital cellulitis and intracranial infection.
METHODS: Six patients diagnosed with and treated for PPT in Pediatric Clinic of Uludag University Faculty of Medicine from 2010 to 2015 were reviewed retrospectively. Age, sex, presenting symptoms and signs, laboratory and radiological findings, as well as intracranial complications and treatment modalities of all patients were evaluated.
RESULTS: The authors present 6 pediatric patients of PPT, 5 males and 1 female with a mean age of 11 years (age range, 7-18 years). All patients presented with headache, fever, and tender frontal swelling. Two of the patients had epidural abscess and 1 had preseptal orbital cellulitis in addition to PPT. All of them had computed tomography scan and/or magnetic resonance imaging. Endoscopic sinus surgery was performed in 4 patients and 2 patients underwent neurosurgical intervention with antibiotherapy.
CONCLUSIONS: Pott puffy tumor may be associated with potentially dangerous intracranial complications. Early diagnosis and treatment are essential to reduce morbidity and mortality. Imaging plays an important role in the diagnosis of the disease and the detection of its complications.

PMID: 27100642 [PubMed - indexed for MEDLINE]

Quetiapine-induced absence seizures in a dementia patient.

Geriatr Gerontol Int. 2016 Oct;16(10):1168-1171

Authors: Shao SC, Wu WH, Yang YK, Lai EC

PMID: 27758061 [PubMed - indexed for MEDLINE]

Bullous pemphigoid and percutaneous endoscopic gastrostomy.

Geriatr Gerontol Int. 2016 Oct;16(10):1173-1174

Authors: Nozu T, Okumura T

PMID: 27758060 [PubMed - indexed for MEDLINE]

Subjective memory complaints and depression as clinical symptoms of disseminated nocardiosis by Nocardia abscessus.

Geriatr Gerontol Int. 2016 Oct;16(10):1167-1168

Authors: Boccardi V, Croce MF, Ruggiero C, Aisa G, Tosti A, Mecocci P

PMID: 27758059 [PubMed - indexed for MEDLINE]

Kawasaki Disease at 50 Years.

JAMA Pediatr. 2016 Nov 01;170(11):1093-1099

Authors: Cohen E, Sundel R

Abstract
Importance: Kawasaki disease (KD) is the most recognized vasculitis of childhood. The condition's characteristic high fever, rash, mucositis, conjunctivitis, lymphadenopathy, and extremity changes are superficially unexceptional, and resolve spontaneously within a mean of 12 days. It is the acuity and the potential for life-changing damage to the coronary arteries that distinguish KD from conditions that mimic it and exemplify the unique aspects and challenges of vascular inflammation in children.
Observations: Although KD is an orphan disease, its role as a leading cause of acquired heart disease in children has led to significant efforts to determine its etiology, optimize diagnosis, and customize treatment according to individuals' needs. The result is that KD can now be controlled without sequelae in more than 95% of cases. Furthermore, advances in stratifying patients according to measurable risk factors allow therapy to be personalized in increasingly effective ways. High-risk patients, such as infants younger than 6 months, those with early evidence of coronary artery dilatation, and those with extreme abnormalities in laboratory test results, are often identified at presentation. This early identification allows them to be treated with corticosteroids in addition to intravenous immunoglobulin to improve their outcomes. Children with similar findings on laboratory tests and echocardiography may be treated based on algorithms for managing "incomplete KD" despite falling short of fulfilling classic diagnostic criteria. Children who do not respond to intravenous immunoglobulin are the focus of trials to minimize the duration of inflammation and thereby protect their coronary arteries in ways never before considered.
Conclusions and Relevance: Kawasaki disease is a hybrid condition at the junction of infectious diseases, immunology, rheumatology, and cardiology. Rather than being left an orphan disease, KD is bringing disciplines together to identify its genetic, pathophysiological, and hemodynamic features. In turn, this work promises to shed light on many other inflammatory conditions as well.

PMID: 27668809 [PubMed - indexed for MEDLINE]

Mutation-specific effects on thin filament length in thin filament myopathy.

Ann Neurol. 2016 Jun;79(6):959-69

Authors: Winter JM, Joureau B, Lee EJ, Kiss B, Yuen M, Gupta VA, Pappas CT, Gregorio CC, Stienen GJ, Edvardson S, Wallgren-Pettersson C, Lehtokari VL, Pelin K, Malfatti E, Romero NB, Engelen BG, Voermans NC, Donkervoort S, Bönnemann CG, Clarke NF, Beggs AH, Granzier H, Ottenheijm CA

Abstract
OBJECTIVE: Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation.
METHODS: We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41.
RESULTS: Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force-sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin-thick filament overlap.
INTERPRETATION: These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. Ann Neurol 2016;79:959-969.

PMID: 27074222 [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 2017/06/07

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 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]