Measuring what matters to rare disease patients - reflections on the work by the IRDiRC taskforce on patient-centered outcome measures.

Orphanet J Rare Dis. 2017 11 02;12(1):171

Authors: Morel T, Cano SJ

Abstract
Our ability to evaluate outcomes which genuinely reflect patients' unmet needs, hopes and concerns is of pivotal importance. However, much current clinical research and practice falls short of this objective by selecting outcome measures which do not capture patient value to the fullest. In this Opinion, we discuss Patient-Centered Outcomes Measures (PCOMs), which have the potential to systematically incorporate patient perspectives to measure those outcomes that matter most to patients. We argue for greater multi-stakeholder collaboration to develop PCOMs, with rare disease patients and families at the center. Beyond advancing the science of patient input, PCOMs are powerful tools to translate care or observed treatment benefit into an 'interpretable' measure of patient benefit, and thereby help demonstrate clinical effectiveness. We propose mixed methods psychometric research as the best route to deliver fit-for-purpose PCOMs in rare diseases, as this methodology brings together qualitative and quantitative research methods in tandem with the explicit aim to efficiently utilise data from small samples. And, whether one opts to develop a brand-new PCOM or to select or adapt an existing outcome measure for use in a rare disease, the anchors remain the same: patients, their daily experience of the rare disease, their preferences, core concepts and values. Ultimately, existing value frameworks, registries, and outcomes-based contracts largely fall short of consistently measuring the full range of outcomes that matter to patients. We argue that greater use of PCOMs in rare diseases would enable a fast track to Patient-Centered Care.

PMID: 29096663 [PubMed - indexed for MEDLINE]

Touraine-Solente-Gole syndrome.

Orbit. 2018 Apr;37(2):97-101

Authors: Doshi D

Abstract
Touraine-Solente-Gole syndrome, also known as Pachydermoperiostosis (PDP) or Primary Hypertrophic Osteoarthropathy, is a rare hereditary disorder, which affects both bones and skin. It is characterized by a combination of dermatologic changes (pachydermia or thickening of the skin) and rheumatologic manifestations (periostosis and finger clubbing). Eyelid ptosis which is caused by thickened eyelids (blepharoptosis) is a less common symptom. We report the case of a patient with a complete form of Touraine-Solente-Gole syndrome with bilateral blepharoptosis as presenting feature.

PMID: 29040027 [PubMed - indexed for MEDLINE]

Orbital T-cell lymphoma versus lupus panniculitits: a T-cell-mediated spectrum of orbital lymphoproliferative disease.

Orbit. 2018 Apr;37(2):102-104

Authors: Huggins AB, Kim C, Rabinowitz MP

Abstract
This is a case description of a single male patient found to have T-cell-mediated inflammation and lymphoproliferation of the orbit. Chronic T-cell-mediated inflammatory disease can pose a diagnostic challenge particularly in its differentiation from a neoplastic process. The histopathology in this case demonstrated features of both lupus erythematosus panniculitis and features of orbital T-cell lymphoma. While both are rare, lupus erythematosus panniculitis of the orbit is even more exceptional; this patient's indolent, chronic relapsing course distinguished itself from the typical aggression of orbital T-cell lymphoma. We believe this rare case may actually represent an example of a newly described disease spectrum that incorporates lupus erythematosus panniculitis as well as subcutaneous panniculitis-like T-cell lymphoma.

PMID: 29039997 [PubMed - indexed for MEDLINE]

KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers.

Orphanet J Rare Dis. 2017 10 16;12(1):163

Authors: Koene S, Spaans E, Van Bortel L, Van Lancker G, Delafontaine B, Badilini F, Beyrath J, Smeitink J

Abstract
BACKGROUND: Mitochondrial disorders are a clinically, biochemically and genetically heterogeneous group of multi-system diseases, with an unmet medical need for treatment. KH176 is an orally bio-available small molecule under development for the treatment of mitochondrial(-related) diseases. The compound is a member of a new class of drugs, acting as a potent intracellular redox-modulating agent essential for the control of oxidative and redox pathologies. The aim of this randomized, placebo controlled, double-blinded phase 1 study was to test safety, tolerability and pharmacokinetics of single and multiple doses of KH176 in healthy male volunteers. Putative effects on redox related biomarkers were explored.
RESULTS: KH176 was well tolerated up to and including a single dose of 800 mg and multiple doses of 400 mg b.i.d. for 7 Days. However, when the QT interval was corrected for heart rate, administration of single doses of 800 and 2000 mg and at a multiple dose of 400 mg KH176 had marked effects. Post-hoc analysis of the ECGs showed clear changes in cardiac electrophysiology at single doses of 800 and 2000 mg and multiple doses of 400 mg b.i.d.. At lower doses, detailed ECG analysis showed no changes in electrophysiology compared to placebo. Exposure-response modelling of the cardiac intervals revealed an exposure range of KH176 without effects on cardiac conduction and provided a threshold of 1000 ng/mL above which changes in intervals could occur. After single- and multiple-dose administration, the pharmacokinetics of KH176 was more than dose proportional. KH176 accumulated to a small extent and food only slightly affected the pharmacokinetics of KH176, which was considered clinically irrelevant. Renal excretion of unchanged KH176 and its metabolite represents a minor pathway in the elimination of KH176. As expected in healthy volunteers no effects on redox biomarkers were observed.
CONCLUSION: The study deemed that KH176 is well tolerated up to single doses of 800 mg and multiple doses of 400 mg b.i.d. and has a pharmacokinetic profile supportive for a twice daily dosing. Only at high doses, KH176 causes clinically relevant changes in cardiac electrophysiology, including prolonged QTc interval and changes in T wave morphology. A Phase 2 clinical trial (100 mg b.i.d., orally) has been conducted recently of which the final results are expected Q1 2018.
TRIAL REGISTRATION: NCT02544217 . Registered. ISRCTN43372293 . Retrospectively registered.

PMID: 29037240 [PubMed - indexed for MEDLINE]

Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic Web Layer.

Biomed Res Int. 2017;2017:8327980

Authors: Sernadela P, González-Castro L, Carta C, van der Horst E, Lopes P, Kaliyaperumal R, Thompson M, Thompson R, Queralt-Rosinach N, Lopez E, Wood L, Robertson A, Lamanna C, Gilling M, Orth M, Merino-Martinez R, Posada M, Taruscio D, Lochmüller H, Robinson P, Roos M, Oliveira JL

Abstract
Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries.

PMID: 29214177 [PubMed - indexed for MEDLINE]

Patient, disease, and treatment factors associated with overall survival in esthesioneuroblastoma.

Int Forum Allergy Rhinol. 2017 Dec;7(12):1186-1194

Authors: Carey RM, Godovchik J, Workman AD, Kuan EC, Parasher AK, Chen J, Palmer JN, Adappa ND, Newman JG, Brant JA

Abstract
BACKGROUND: Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single-institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions.
METHODS: The NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival.
RESULTS: A total of 1225 patients with ENB met the inclusion criteria. The 5-year overall survival was 76.2% (95% confidence interval [CI], 73.4-79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender (p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all-cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40-0.95). Surgery with chemotherapy alone was associated with increased odds of all-cause mortality (OR, 4.86; 95% CI, 2.31-10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07-8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24-0.81).
CONCLUSION: The most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re-evaluated in further studies.

PMID: 29045018 [PubMed - indexed for MEDLINE]

Uncovering novel repositioning opportunities using the Open Targets platform.

Drug Discov Today. 2017 Dec;22(12):1800-1807

Authors: Khaladkar M, Koscielny G, Hasan S, Agarwal P, Dunham I, Rajpal D, Sanseau P

Abstract
The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases. We have harnessed the integrated data from this platform for novel drug repositioning opportunities. Our computational workflow systematically mines data from various evidence categories and presents potential repositioning opportunities for drugs that are marketed or being investigated in ongoing human clinical trials, based on evidence strength on target-disease pairing. We classified these novel target-disease opportunities in several ways: (i) number of independent counts of evidence; (ii) broad therapy area of origin; and (iii) repositioning within or across therapy areas. Finally, we elaborate on one example that was identified by this approach.

PMID: 28919242 [PubMed - indexed for MEDLINE]

Reconstructing normality following the diagnosis of a childhood chronic disease: does "rare" make a difference?

Eur J Pediatr. 2018 Apr;177(4):489-495

Authors: Germeni E, Vallini I, Bianchetti MG, Schulz PJ

Abstract
Living with a childhood chronic disease can be challenging, especially if the diagnosis involves a rare condition. This study sought to elucidate how the diagnosis of a rare disease, as compared to a common, chronic condition, may influence maternal experiences of childhood illness. We conducted face-to-face, semi-structured interviews with 26 mothers of children treated in a pediatric hospital in the province of Lecco, Italy. Half of the participants had a child diagnosed with Bartter syndrome (BS), and the rest had a child suffering from celiac disease (CD). Interviews were recorded, transcribed, and analyzed using an inductive thematic approach. We identified three main themes from the analysis of our data: (1) disrupted normality and the need to know, (2) reconstructing normality, and (3) acting "normal." Although most participants experienced the disclosure of diagnosis as a relief, processes that facilitated normality reconstruction in celiac families, notably access to appropriate information, social support, and personal contact with comparison others, were found to be important stressors for mothers living with BS.
CONCLUSION: This comparative qualitative study provides evidence on how well-known problems associated with the rarity of childhood diseases impact on families' efforts to cope with the illness and regain a sense of normality. What is Known: • Families living with a rare disease have been found to experience a range of common problems, directly linked to the rarity of these pathologies. What is New: • Maximization of both emotional and instrumental social support, through provision of appropriate information or establishment of disease-specific support groups, could greatly contribute to rare disease families' efforts to cope with childhood illness and regain a sense of normality.

PMID: 29335841 [PubMed - indexed for MEDLINE]

An unusually large osteochondroma of the mandibular angle: a case report.

World J Surg Oncol. 2017 Nov 13;15(1):201

Authors: Abe R, Miyamoto I, Sato H, Saitou D, Yamaya G, Yamada H

Abstract
BACKGROUND: Osteochondroma is a benign bone tumor that can occur in both the mesenchymal and craniofacial bones. However, craniofacial osteochondromas are extremely rare, because the mandible develops by intramembranous ossification rather than by endochondral ossification.
CASE PRESENTATION: The most common site of craniofacial osteochondroma is the mandibular condyle, followed by the coronoid process. In the present study, we have described the case of a 64-year-old Japanese man with an unusually large osteochondroma located on the internal angle of the mandibular body. Clinical, radiological, pathological, and treatment-related aspects are discussed with respect to the tumor origins.
CONCLUSIONS: In the medical literature, there have been few reports of large osteochondromas of the mandibular angle with no clinical symptoms.

PMID: 29132383 [PubMed - indexed for MEDLINE]

DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome.

Hum Mutat. 2018 Jan;39(1):23-39

Authors: Marsh APL, Edwards TJ, Galea C, Cooper HM, Engle EC, Jamuar SS, Méneret A, Moutard ML, Nava C, Rastetter A, Robinson G, Rouleau G, Roze E, Spencer-Smith M, Trouillard O, Billette de Villemeur T, Walsh CA, Yu TW, IRC5 Consortium, Heron D, Sherr EH, Richards LJ, Depienne C, Leventer RJ, Lockhart PJ

Abstract
The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome (DSBS). Although the underlying molecular mechanisms leading to disease remain poorly understood, they are thought to stem from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC mutations associated with abnormal CNS development in humans, including 14 missense and 12 predicted loss-of-function mutations, and discuss their associated clinical characteristics and diagnostic features. We provide an update on the observed genotype-phenotype relationships of congenital mirror movements, isolated ACC and DSBS, and correlate this to our current understanding of the biological function of DCC in the development of the CNS. All mutations and their associated phenotypes were deposited into a locus-specific LOVD (https://databases.lovd.nl/shared/genes/DCC).

PMID: 29068161 [PubMed - indexed for MEDLINE]

30 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 2018/07/17

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.

Regulating Rare Disease: Safely Facilitating Access to Orphan Drugs.

Fordham Law Rev. 2018 Mar;86(4):1889-921

Authors: Bannister JB

Abstract
While approximately one in ten Americans suffers from a rare disease, only 5 percent of rare diseases have a U.S. Food and Drug Administration (FDA) approved treatment. Congressional and regulatory efforts to stimulate the development of rare-disease treatments, while laudable, have not resolved the fundamental issues surrounding rare-disease treatment development. Indeed, small patient populations, incomplete scientific understanding of rare diseases, and high development costs continually limit the availability of rare-disease treatments. To illustrate the struggle of developing and approving safe rare-disease treatments, this Note begins by discussing the approval of Eteplirsen, the first drug approved for treating a rare disease called Duchenne muscular dystrophy. After exploring the current drug regulation system and how this impacts the availability of rare-disease treatments, this Note examines the 21st Century Cures Act's patient experience data provisions and the currently pending Trickett Wendler Right to Try Act. Ultimately, the unmet therapeutic needs of rare-disease patients can be met while protecting patient safety. This Note reasons that, if carefully implemented, the 21st Century Cures Act and the Trickett Wendler Right to Try Act could work in tandem to safely facilitate patient access to rare-disease treatments.

PMID: 29993206 [PubMed - indexed for MEDLINE]

Retrovesical malignant fibrous histiocytoma: a rare tumor.

BMJ Case Rep. 2017 Dec 02;2017:

Authors: Pathak S, Soni TP, Gupta AK, Sharma LM

Abstract
Malignant fibrous histiocytoma (MFH) originating from the retrovesical space is a very rare tumour. A 61-year-old man presented to our hospital with complaints of retention of urine and burning sensation during micturition since 6 months. CT scan abdomen showed a large retrovesical mass between the urinary bladder and rectum, measuring 11×9×12 cm, displacing the urinary bladder. Serum PSA (Prostate Specific Antigen) value was within normal range. Biopsy from retrovesical mass and immunohistochemistry was suggestive of MFH. Wide excision of the retrovesical mass was done. Histopathology confirmed the diagnosis of MFH. He received adjuvant radiotherapy. He is on regular follow-up since the last 2 years after radiotherapy with no signs and symptoms of disease recurrence.

PMID: 29197849 [PubMed - indexed for MEDLINE]

Prior opioid exposure influences parents' sharing of their children's CYP2D6 research results.

Pharmacogenomics. 2017 Aug;18(13):1199-1213

Authors: Myers MF, Zhang X, McLaughlin B, Kissell D, Perry CL, Veerkamp M, Zhang K, Holm IA, Prows CA

Abstract
AIM: To determine parents' use of their children's CYP2D6 research result. We hypothesized that perceived utility, likelihood of sharing and actual sharing of results would differ between parents with children previously exposed (cases) or unexposed (controls) to opioids.
METHODS: We returned results by phone (baseline). We surveyed parents about perceived utility and likelihood of sharing their child's research result at baseline, and actual sharing at 3 and 12 months.
RESULTS: Cases were more likely than controls to agree that they (p = 0.022) and the doctors (p = 0.041) could use the results to care for their child, to report higher likelihood of sharing (p = 0.042) and to actually share results with the child's doctor (p = 0.026).
CONCLUSION: Prior opioid exposure influenced perceived clinical utility and sharing behaviors.

PMID: 28745549 [PubMed - indexed for MEDLINE]

Anaplastic Large T-Cell Lymphoma Associated with Breast Implants - Rare Disease.

Isr Med Assoc J. 2017 Jun;19(6):390-392

Authors: Ben-Nun O, Bitterman N, Tadmor T, Bejar J, Shalata A, Yarin H, Calderon N

PMID: 28647941 [PubMed - indexed for MEDLINE]

Mental Health and Well-Being in Mothers of Children With Rare Genetic Syndromes Showing Chronic Challenging Behavior: A Cross-Sectional and Longitudinal Study.

Am J Intellect Dev Disabil. 2018 05;123(3):241-253

Authors: Adams D, Clarke S, Griffith G, Howlin P, Moss J, Petty J, Tunnicliffe P, Oliver C

Abstract
It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.

PMID: 29671635 [PubMed - indexed for MEDLINE]

A Case of Kleine-Levin Syndrome: Diagnostic and Therapeutic Challenge.

Acta Med Iran. 2018 Jan;56(1):62-66

Authors: Marčić M, Marčić L, Titlić M

Abstract
Kleine-Levin syndrome (KLS) is a rare sleep disorder mainly affecting teenage boys in which the main features are intermittent hypersomnolence, behavioral and cognitive disturbances, hyperphagia, and in some cases hyper sexuality. Etiology is unknown, and there is no specific clinical or imaging test for this syndrome even though the illness has well-defined clinical features. Also, there is no effective treatment for KLS. KLS is self-limited, so the prognosis for these patients is not so bad. This study presents our case report and comprehensive workout that led to diagnosis which is primarily clinical. Our patient is a 20-year-old man referred to our clinic because of sleeping problems. At the age of 14, he presented with complaints of the excessive duration of sleep, increased appetite, excessive daytime sleepiness, loss of interest in social activities during attendance of high school and hallucinations. The excessive diagnostic procedure does not find pathological. Kleine-Levin syndrome (KLS) is a rare sleep disorder of unknown etiology which diagnosis is clinical and diagnostic workup is mainly to exclude other similar conditions. There is no specific therapy, but the disease is self-limited and with good prognosis.

PMID: 29436797 [PubMed - indexed for MEDLINE]

Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency.

Mol Genet Metab Rep. 2018 Sep;16:15-19

Authors: Fan X, Xie B, Zou J, Luo J, Qin Z, D'Gama AM, Shi J, Yi S, Yang Q, Wang J, Luo S, Chen S, Agrawal PB, Li Q, Shen Y

Abstract
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism caused by mutations in EFTA, EFTB, or ETFDH. Many MADD patients are responsive to treatment with riboflavin, termed riboflavin-responsive MADD (RR-MADD). Here, we report three novel mutations and one previously reported mutation in ETFDH in four RR-MADD patients who presented at various ages, and characterize the corresponding changes in ETF-QO protein structure. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD, and may not only prevent patients from invasive testing, but also allow timely initiation of riboflavin treatment. The novel variants in ETFDH and the corresponding clinical features reported here enrich the allelic heterogeneity of RR-MADD and provide insight into genotype-phenotype relationships.

PMID: 29988809 [PubMed]

The BabySeq project: implementing genomic sequencing in newborns.

BMC Pediatr. 2018 Jul 09;18(1):225

Authors: Holm IA, Agrawal PB, Ceyhan-Birsoy O, Christensen KD, Fayer S, Frankel LA, Genetti CA, Krier JB, LaMay RC, Levy HL, McGuire AL, Parad RB, Park PJ, Pereira S, Rehm HL, Schwartz TS, Waisbren SE, Yu TW, BabySeq Project Team, Green RC, Beggs AH

Abstract
BACKGROUND: The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The "BabySeq Project" is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.
METHODS: Families of newborns are enrolled from Boston Children's Hospital and Brigham and Women's Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.
DISCUSSION: The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.
TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov Identifier: NCT02422511 . Registration date: 10 April 2015.

PMID: 29986673 [PubMed - in process]

RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes.

PLoS Genet. 2018 03;14(3):e1007226

Authors: Bennett AH, O'Donohue MF, Gundry SR, Chan AT, Widrick J, Draper I, Chakraborty A, Zhou Y, Zon LI, Gleizes PE, Beggs AH, Gupta VA

Abstract
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles.

PMID: 29518074 [PubMed - indexed for MEDLINE]