7 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 2017/03/28

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.

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research.

Cell. 2017 Mar 23;169(1):6-12

Authors: Manolio TA, Fowler DM, Starita LM, Haendel MA, MacArthur DG, Biesecker LG, Worthey E, Chisholm RL, Green ED, Jacob HJ, McLeod HL, Roden D, Rodriguez LL, Williams MS, Cooper GM, Cox NJ, Herman GE, Kingsmore S, Lo C, Lutz C, MacRae CA, Nussbaum RL, Ordovas JM, Ramos EM, Robinson PN, Rubinstein WS, Seidman C, Stranger BE, Wang H, Westerfield M, Bult C

Abstract
Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations, we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing.

PMID: 28340351 [PubMed - in process]

[Not Available].

Rofo. 2016 Jul;188(7):687-9

Authors: Kunz WG, Paprottka PM, Reichelt A

PMID: 27355634 [PubMed - indexed for MEDLINE]

[Not Available].

Rofo. 2016 Jul;188(7):684-5

Authors: Peters S, Cohrs G, Larsen N

PMID: 27355632 [PubMed - indexed for MEDLINE]

ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.

Brain. 2017 Mar 01;:

Authors: Anttonen AK, Laari A, Kousi M, Yang YJ, Jääskeläinen T, Somer M, Siintola E, Jakkula E, Muona M, Tegelberg S, Lönnqvist T, Pihko H, Valanne L, Paetau A, Lun MP, Hästbacka J, Kopra O, Joensuu T, Katsanis N, Lehtinen MK, Palvimo JJ, Lehesjoki AE

Abstract
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing. The identified mutation affects a highly conserved amino acid residue in the zinc finger domain of ZNHIT3. Both knockdown and genome editing of znhit3 in zebrafish embryos recapitulate the patients' cerebellar defects, microcephaly and oedema. These phenotypes are rescued by wild-type, but not mutant human ZNHIT3 mRNA, suggesting that the patient missense substitution causes disease through a loss-of-function mechanism. Transfection of cell lines with ZNHIT3 expression vectors showed that the PEHO syndrome mutant protein is unstable. Immunohistochemical analysis of mouse cerebellar tissue demonstrated ZNHIT3 to be expressed in proliferating granule cell precursors, in proliferating and post-mitotic granule cells, and in Purkinje cells. Knockdown of Znhit3 in cultured mouse granule neurons and ex vivo cerebellar slices indicate that ZNHIT3 is indispensable for granule neuron survival and migration, consistent with the zebrafish findings and patient neuropathology. These results suggest that loss-of-function of a nuclear regulator protein underlies PEHO syndrome and imply that establishment of its spatiotemporal interaction targets will be the basis for developing therapeutic approaches and for improved understanding of cerebellar development.

PMID: 28335020 [PubMed - as supplied by publisher]

A Rare Congenital Pulmonary Anomaly of a Young Adult: Pseudosequestration.

Ann Thorac Surg. 2016 Aug;102(2):e163

Authors: Özdil A, Akçam Tİ, Çağırıcı U, Savaş R

PMID: 27449457 [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 2017/03/23

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 life-threatening condition: metastasis to the heart.

Am J Emerg Med. 2016 Sep;34(9):1912.e3-4

Authors: Topcu S, Gülcü O, Aksu U, Aksakal E

PMID: 26922641 [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 2017/03/18

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.

AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant.

Cold Spring Harb Mol Case Stud. 2017 Mar;3(2):a001560

Authors: Morton SU, Prabhu SP, Lidov HG, Shi J, Anselm I, Brownstein CA, Bainbridge MN, Beggs AH, Vargas SO, Agrawal PB

Abstract
Apoptosis-inducing factor mitochondrion-associated 1 (AIFM1), encoded by the gene AIFM1, has roles in electron transport, apoptosis, ferredoxin metabolism, reactive oxygen species generation, and immune system regulation. Here we describe a patient with a novel AIFM1 variant presenting unusually early in life with mitochondrial disease, rapid deterioration, and death. Autopsy, at the age of 4 mo, revealed features of mitochondrial encephalopathy, myopathy, and involvement of peripheral nerves with axonal degeneration. In addition, there was microvesicular steatosis in the liver, thymic noninvolution, follicular bronchiolitis, and pulmonary arterial medial hypertrophy. This report adds to the clinical and pathological spectrum of disease related to AIFM1 mutations and provides insights into the role of AIFM1 in cellular function.

PMID: 28299359 [PubMed - in process]

7 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 2017/03/16

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.

A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop.

J Clin Neuromuscul Dis. 2017 Mar;18(3):147-151

Authors: Karakaya M, Ceyhan-Birsoy O, Beggs AH, Topaloglu H

Abstract
Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases of the neuromuscular junction caused by compromised synaptic transmission. Clinical features include early-onset weakness of limbs and oculobulbar muscles resulting in hypotonia, bulbar paresis, ptosis, and hypoventilation. The first dropped head syndrome in children were detected in 2 patients with LMNA and SEPN1 mutations. We report a 17-month-old boy with dropped head and limb-girdle weakness, who had no ptosis or ophthalmoplegia at presentation. We performed whole exome sequencing, which revealed a homozygous missense variant in the AGRN gene c.5023G>A, p.Gly1675Ser in the LG2 domain, which is predicted to be likely disease causing by in silico tools. Agrin is known to play a critical role in the development and maintenance of the neuromuscular junction. Agrin-related CMS is one of the rarest subtypes. Of note, our patient is the first described patient with agrin-related CMS with dropped head phenotype.

PMID: 28221305 [PubMed - indexed for MEDLINE]

Giant Interfrontal Encephalocele in an Infant: A Rare Entity.

Pediatr Neurosurg. 2016;51(6):309-312

Authors: Faheem M, Singh SK, Ojha BK, Chandra A, Srivastava C, Jaiswal M, Zeeshan Q

Abstract
Interfrontal encephalocele is one of the rare varieties of anterior encephalocele, and a giant interfrontal encephalocele is extremely rare. The authors could find only one case report of giant interfrontal encephalocele in the literature. Anterior encephaloceles are more prevalent in South-East Asia and some northern parts of India. Giant encephalocele poses a great challenge to neurosurgeons and neuroanesthetists during surgery, as these infants usually have a low birth weight and a large sac, thus making the infant prone to hypothermia and blood loss among other risks. We encountered a patient with a giant interfrontal encephalocele aged 1 month. The rarity of this case prompted us to this report.

PMID: 27513987 [PubMed - indexed for MEDLINE]

Determinants and Equity Evaluation for Health Expenditure Among Patients with Rare Diseases in China.

Chin Med J (Engl). 2016 Jun 20;129(12):1387-93

Authors: Xin XX, Zhao L, Guan XD, Shi LW

Abstract
BACKGROUND: China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity.
METHODS: Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket (OOP) health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve.
RESULTS: Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female (P = 0.048), over 50 years of age (P = 0.062), high-income group (P = 0.021), hospitalization (P = 0.000), and reimbursement ratio (RR) (P = 0.000) were positively correlated with total health expenditure. Diseases not needing long-term treatment (P = 0.000) was negatively correlated with total health expenditure. Over 50 years of age (P = 0.065), high-income group (P = 0.018), hospitalization (P = 0.000) and having Urban Employee Basic Medical Insurance (UEBMI) (P = 0.022) were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education (P = 0.044 and P = 0.081) and reimbursement ratio (P = 0.078) were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively.
CONCLUSIONS: OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people.

PMID: 27270531 [PubMed - indexed for MEDLINE]

The role of registries in rare genetic lipid disorders: Review and introduction of the first global registry in lipoprotein lipase deficiency.

Atherosclerosis. 2016 Aug 21;:

Authors: Steinhagen-Thiessen E, Stroes E, Soran H, Johnson C, Moulin P, Iotti G, Zibellini M, Ossenkoppele B, Dippel M, Averna MR, GENIALL Investigators

Abstract
A good understanding of the natural history of rare genetic lipid disorders is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive lipid disorder characterized by severe hypertriglyceridemia and a very high risk for recurrent acute pancreatitis, however, only limited data are available on its natural course. Alipogene tiparvovec (Glybera(®)) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan. The aim of this publication is to introduce the GENIALL Registry within a structured literature review of registries in rare genetic lipid disorders. A total of 11 relevant initiatives/registries were identified (homozygous Familial Hypercholesterolemia (hoFH) [n = 5]; LPLD [n = 1]; Lysosomal Acid Lipase Deficiency [LALD, n = 1], detection of mutations in genetic lipid disorders [n = 4]). Besides one product registry in hoFH and the LALD registry, all other initiatives are local or country-specific. GENIALL is the first global prospective registry in LPLD that will collect physician and patient generated data on the natural course of LPLD, as well as long-term outcomes of gene therapy.
CONCLUSION: There is a limited number of international initiatives focusing on the natural course of specific rare genetic lipid disorders. The GENIALL LPLD Registry could be the first step towards a future broader global initiative that collects data related to familial chylomicronemia syndrome and their underlying genetic causes.

PMID: 28284702 [PubMed - as supplied by publisher]

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU.

Hum Genet. 2017 Mar 10;:

Authors: Depienne C, Nava C, Keren B, Heide S, Rastetter A, Passemard S, Chantot-Bastaraud S, Moutard ML, Agrawal PB, VanNoy G, Stoler JM, Amor DJ, Billette de Villemeur T, Doummar D, Alby C, Cormier-Daire V, Garel C, Marzin P, Scheidecker S, de Saint-Martin A, Hirsch E, Korff C, Bottani A, Faivre L, Verloes A, Orzechowski C, Burglen L, Leheup B, Roume J, Andrieux J, Sheth F, Datar C, Parker MJ, Pasquier L, Odent S, Naudion S, Delrue MA, Le Caignec C, Vincent M, Isidor B, Renaldo F, Stewart F, Toutain A, Koehler U, Häckl B, von Stülpnagel C, Kluger G, Møller RS, Pal D, Jonson T, Soller M, Verbeek NE, van Haelst MM, de Kovel C, Koeleman B, Monroe G, van Haaften G, DDD Study, Attié-Bitach T, Boutaud L, Héron D, Mignot C

Abstract
Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.

PMID: 28283832 [PubMed - as supplied by publisher]

Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation.

Cell. 2017 Mar 09;168(6):1053-1064.e15

Authors: Kim AR, Ulirsch JC, Wilmes S, Unal E, Moraga I, Karakukcu M, Yuan D, Kazerounian S, Abdulhay NJ, King DS, Gupta N, Gabriel SB, Lander ES, Patiroglu T, Ozcan A, Ozdemir MA, Garcia KC, Piehler J, Gazda HT, Klein DE, Sankaran VG

Abstract
Cytokines are classically thought to stimulate downstream signaling pathways through monotonic activation of receptors. We describe a severe anemia resulting from a homozygous mutation (R150Q) in the cytokine erythropoietin (EPO). Surprisingly, the EPO R150Q mutant shows only a mild reduction in affinity for its receptor but has altered binding kinetics. The EPO mutant is less effective at stimulating erythroid cell proliferation and differentiation, even at maximally potent concentrations. While the EPO mutant can stimulate effectors such as STAT5 to a similar extent as the wild-type ligand, there is reduced JAK2-mediated phosphorylation of select downstream targets. This impairment in downstream signaling mechanistically arises from altered receptor dimerization dynamics due to extracellular binding changes. These results demonstrate how variation in a single cytokine can lead to biased downstream signaling and can thereby cause human disease. Moreover, we have defined a distinct treatable form of anemia through mutation identification and functional studies.

PMID: 28283061 [PubMed - in process]

Splenic rupture and mediastinal mass associated with rare TdT-negative T-LBL/T-ALL lead to sudden death of a juvenile.

Forensic Sci Med Pathol. 2016 Dec;12(4):523-526

Authors: Gascho D, Huber B, Bolliger SA, Thali MJ, Schaerli S

PMID: 27778145 [PubMed - indexed for MEDLINE]

An extreme case of platypnoea-orthodeoxia syndrome.

Clin Med (Lond). 2016 Oct;16(5):453-454

Authors: O'Gallagher K, Chou E, Jeyabraba S, Sinha A, Robb D, Byrne J

Abstract
An 80-year-old female presented with progressive breathlessness, worse on sitting or standing and relieved by lying flat. Subsequent investigations identified a patent foramen ovale (PFO) with right-to-left flow across the interatrial septum (IAS). A diagnosis of platypnoea orthodeoxia syndrome secondary to inter-atrial shunting was made. Technical features precluded a percutaneous PFO closure so an open surgical repair was performed with complete resolution of symptoms. We discuss the pathophysiology and management of platypnoea orthodeoxia syndrome.

PMID: 27697809 [PubMed - indexed for MEDLINE]

The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry.

Int J Artif Organs. 2017 Mar 07;40(1):40-42

Authors: Walpoth BH, Meyer M, Gaudet-Blavignac C, Baumann P, Gilquin P, Lovis C

Abstract
Accidental hypothermia could be listed as an 'orphan disease,' since mild hypothermia is common but has no severe medical consequences, whereas severe hypothermia is rare and life-threatening. In order to increase our knowledge, find new outcome predictors, and propose better guidelines for the treatment of deep accidental hypothermia victims, we created the International Hypothermia Registry (IHR: https://www.hypothermia-registry.org), which will allow us to gather a large number of cases in order to achieve statistical significance and issue evidence-based recommendations.

PMID: 28277601 [PubMed - as supplied by publisher]