The importance of review articles in making the voice of rare diseases heard: OJRD's 10th anniversary.

Orphanet J Rare Dis. 2016;11(1):71

Authors: Aymé S

PMID: 27234175 [PubMed - as supplied by publisher]

Perirenal Involvement of Mantle Cell Lymphoma: Imaging Features.

Urology. 2016 May 24;

Authors: Ufuk F, Karaman E, Karabulut N

Abstract
Perirenal lymphoma is a rare disease and accouning for less than 10% of all malignant lymphomas. Mantle cell lymphoma (MCL) is the rarest but one of the most aggressive non-Hodgkin's lymphoma (NHL) subtype. The perirenal involvement of MCL has not been reported previously. A 69-year-old male, who had been diagnosed as having mantle cell lymphoma (MCL) one year ago, presented with recent-onset right back pain. Herein we present the key imaging findings of perirenal soft tissue manifestation of MCL.

PMID: 27233934 [PubMed - as supplied by publisher]

GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype.

Am J Med Genet A. 2016 May 27;

Authors: Lee JS, Yoo Y, Lim BC, Kim KJ, Song J, Choi M, Chae JH

Abstract
There have been a few reports of GM3 synthase deficiency since the disease of the ganglioside biosynthetic pathway was first reported in 2004. It is characterized by infantile-onset epilepsy with severe intellectual disability, blindness, cutaneous dyspigmentation, and choreoathetosis. Here we report the cases of two Korean female siblings with ST3GAL5 variants, who presented with a Rett-like phenotype. They had delayed speech, hand stereotypies with a loss of purposeful hand movements, and choreoathetosis, but no clinical seizures. One of them had microcephaly, while the other had small head circumference less than 10th centile. There were no abnormal laboratory findings with the exception of a high lactate level. MECP2/CDKL5/FOXG1 genetic tests with an array comparative genomic hybridization revealed no molecular defects. Through whole-exome sequencing of the proband, we found compound heterozygous ST3GAL5 variants (p.Gly201Arg and p.Cys195Ser), both of which were novel. The siblings were the same compound heterozygotes and their unaffected parents were heterozygous carriers of each variant. Liquid chromatography-mass spectrometry analysis confirmed a low level of GM3 and its downstream metabolites, indicating GM3 synthase deficiency. These cases expanded the clinical and genetic spectrum of the ultra-rare disease, GM3 synthase deficiency with ST3GAL5 variants. © 2016 Wiley Periodicals, Inc.

PMID: 27232954 [PubMed - as supplied by publisher]

Research advances on medical genetics in China in 2015.

Yi Chuan. 2016 May 20;38(5):363-390

Authors: Yuanfeng L, Yubo H, Pengbo C, Jinfeng M, Haibei L, Geng Q, Feng Z, Guangfu J, Yong Y, Lingqian W, Jie P, Gangqiao Z

Abstract
Steady progress has been achieved in the medical genetics in China in 2015, as numerous original researches were published in the world's leading journals. Chinese scientists have made significant contributions to various fields of medical genetics, such as pathogenicity of rare diseases, predisposition of common diseases, somatic mutations of cancer, new technologies and methods, disease-related microRNAs (miRNAs), disease-related long non-coding RNAs (lncRNAs), disease-related competing endogenous RNAs (ceRNAs), disease-related RNA splicing and molecular evolution. In these fields, Chinese scientists have gradually formed the tendency, from common variants to rare variants, from single omic analyses to multipleomics integration analyses, from genetic discovery to functional confirmation, from basic research to clinical application. Meanwhile, the findings of Chinese scientists have been drawn great attentions of international peers. This review aims to provide an overall picture of the front in Chinese medical genetics, and highlights the important findings and their research strategy.

PMID: 27232486 [PubMed - as supplied by publisher]

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Nat Commun. 2016;7:11601

Authors: Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, Woltjer RL, Eaton S, Gregory A, Sanford L, Kara E, Houlden H, Cuno SM, Prokisch H, Valletta L, Tiranti V, Younis R, Maher ER, Spencer J, Straatman-Iwanowska A, Gissen P, Selim LA, Pintos-Morell G, Coroleu-Lletget W, Mohammad SS, Yoganathan S, Dale RC, Thomas M, Rihel J, Bodamer OA, Enns CA, Hayflick SJ, Clayton PT, Mills PB, Kurian MA, Wilson SW

Abstract
Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.

PMID: 27231142 [PubMed - in process]

Intradural synovial cyst of the atlantoaxial joint: a case report.

Acta Neurochir (Wien). 2016 May 27;

Authors: Hartmann S, Tschugg A, Kavakebi P, Thomé C

Abstract
BACKGROUND: Intradural synovial cysts of the cervical spine represent a rare disease entity, causing stenosis of the spinal canal and thereby leading to progressive myelopathy. In particular, at the cranio-cervical junction early intervention is necessary to prevent permanent neurological dysfunction. We present the case of a 74-year-old man who presented with moderate cervicogenic headache, gait disturbance and progressive left-sided weakness. Magnetic resonance imaging (MRI) of the cervical spine confirmed a left-sided cystic mass located anteriorly at the craniovertebral junction compressing the surrounding structures.
METHOD: Surgical decompression was performed by means of a minimal left-sided laminectomy of C1. Postoperatively, the patients symptoms slowly improved, albeit a persistent ataxic gait.
RESULTS: Intraoperatively, a large intradural cyst was removed via a minimal suboccipital craniectomy combined with laminectomy of C1. Histopathological evaluation revealed a synovial cyst without any features of neoplasia. Despite not using craniocervical instrumentation, no clinical or radiological signs of atlantoaxial instability were observed up to 2 years after surgery.
CONCLUSIONS: Cystic lesions located at the atlanto-axial joint are a rare cause of cervical myelopathy. Preoperative imaging of the cervical spine should include not only MRI and computerised tomography (CT) but also dynamic imaging. Dorsal decompression without instrumentation prevents progressive neurological decline and may allow cord function to recover. If there is additional preoperative instability, instrumentation and fusion may be necessary.

PMID: 27230912 [PubMed - as supplied by publisher]

Spatial analysis of gender variation in the prevalence of hypertension among the middle-aged and elderly population in Zhejiang Province, China.

BMC Public Health. 2016;16(1):447

Authors: Xu L, Lai D, Fang Y

Abstract
BACKGROUND: Previous studies have shown that there may be gender disparities in the prevalence of hypertension; however, these studies do not address the spatial information contained in the sample which may limit the analytical results. Our study extends the existing Shared Component Model (SCM) and compares its utility with a logistic regression model to evaluate the significance of spatial information for identifying risk factors for hypertension and other non-rare diseases.
METHODS: A total of 1267 residents aged 45 years of age and over were included in our study, of which 48.1 % were males. The overall prevalence of hypertension was 33.2 %, with females experiencing a higher prevalence than males (35.5 % vs. 30.6 %). The research variables included body mass index (BMI), Waist -to-Height Ratio (WHtR), smoking status, alcohol consumption etc. The extended SCM is employed to investigate regional gender variations in the risk of hypertension and assess the gender variation in the middle-aged and elderly populations of Zhejiang Province in eastern China and then its performance is compared with that of a traditional multiple logistic regression model.
RESULTS: Our SCM analysis determined that the spatial pattern of hypertension risk for the middle-aged and elderly populations of Zhejiang Province in eastern China is quite different for males and females. Furthermore, Waist -to-Height Ratio (WHtR) continues to be a simple and effective predictor of hypertension risk for males at the regional level.
CONCLUSIONS: We believe that the extended SCM spatial model is a useful tool for identifying risk factors at the regional level.

PMID: 27230660 [PubMed - in process]

Feasibility and Success Rate of a Fetal MRI and MR Spectroscopy Research Protocol Performed at Term Using a 3.0-Tesla Scanner.

Fetal Diagn Ther. 2016 May 27;

Authors: Sanz Cortes M, Bargallo N, Arranz A, Simoes R, Figueras F, Gratacos E

Abstract
OBJECTIVES: To report the feasibility and main factors affecting the success of a fetal magnetic resonance imaging (MRI) and MR spectroscopy (MRS) research protocol performed at term using a 3-tesla scanner.
METHODS: Pregnant patients at term underwent an MRI. Specific measures were taken to prevent maternal discomfort and distress, such as detailed counseling and maternal repositioning if needed. MRS data were acquired from the frontal lobe and basal ganglia, and processed applying quality control criteria.
RESULTS: The mean gestational age at MRI was 37.4 ± 0.9 weeks. From a total of 245 patients that showed up for the MRI, 11 referred claustrophobia which prevented the test from starting, and 30 patients started the test but decided to discontinue due to discomfort. Thus, the examination was complete in 204 patients. MRS data could be obtained in 170 cases from the frontal lobe and 165 cases from the basal ganglia, of which 52.4 and 68.6%, respectively, complied with our defined quality criteria. The mean scanning time was 34:16 ± 9:30 min:s after excluding those cases presenting initial intolerance to the test. Minor abnormalities were described in 11 MRI reports.
CONCLUSIONS: The fetal MRI/MRS protocol was feasible and generally well tolerated at term on a 3-tesla scanner, but a significant number of cases were lost to analysis. The rate of patients that eventually provided usable research information was 95.5% for anatomical examination and 52.4-68.6% for MRS. This information should be taken into account in the design of fetal brain MRI studies.

PMID: 27230519 [PubMed - as supplied by publisher]

Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada.

Eur Respir J. 2016 May 26;

Authors: Hopkins RB, Burke N, Fell C, Dion G, Kolb M

Abstract
Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation.We used mandatory national administrative data from 2007-2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life.For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease.Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited.

PMID: 27230442 [PubMed - as supplied by publisher]

Achieving optimal cancer outcomes in East Africa through multidisciplinary partnership: a case study of the Kenyan National Retinoblastoma Strategy group.

Global Health. 2016;12(1):23

Authors: Hill JA, Kimani K, White A, Barasa F, Livingstone M, Gallie BL, Dimaras H, Daisy’s Eye Cancer Fund & The Kenyan National Retinoblastoma Strategy Group

Abstract
BACKGROUND: Strategic, interdisciplinary partnerships are essential to addressing the complex drivers of health inequities that result in survival disparities worldwide. Take for example the aggressive early childhood eye cancer retinoblastoma, where survival reaches 97 % in resource-rich countries, but is as low 30 % in some resource-limited nations, where 92 % of the burden lies. This suggests a need for a multifaceted approach to achieve a tangible and sustainable increase in survival.
METHODS: We assembled the history the Kenyan National Retinoblastoma Strategy (KNRbS), using information documented in NGO reports, grant applications, news articles, meeting agendas and summaries. We evaluated the KNRbS using the principles found in the guide for transboundary research partnerships developed by the Swiss Commission for Research Partnerships with Developing Countries.
RESULTS: A nationally co-ordinated approach drawing input and expertise from multiple disciplines and sectors presented opportunities to optimise cure of children with retinoblastoma. Annual meetings were key to achieving the over 40 major outputs of the group's efforts, related to Awareness, Medical Care, Family Support and Resource Mobilization. Three features were found to be critical to the KNRbS success: multidisciplinarity, consistency and flexibility.
CONCLUSION: The KNRbS has achieved a number of key outputs with limited financial investment. As a partnership, the KNRbS meets most of the criteria identified for success. Challenges remain in securing the long-term sustainability of its achievements. Elements of the Kenyan National Retinoblastoma Strategy may be useful to other developing countries struggling with limited survival of retinoblastoma and other cancers or rare diseases.

PMID: 27229322 [PubMed - in process]

Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries.

Orphanet J Rare Dis. 2015;10:80

Authors: Bosch AM, Burlina A, Cunningham A, Bettiol E, Moreau-Stucker F, Koledova E, Benmedjahed K, Regnault A

Abstract
BACKGROUND: The strict and demanding dietary treatment and mild cognitive abnormalities seen in PKU treated from a young age can be expected to affect the health-related quality of life (HRQoL) of patients and their families. Our aim was to describe the HRQoL of patients with PKU from a large international study, using generic HRQoL measures and an innovative PKU-specific HRQoL questionnaire (PKU-QOL). Analyses were exploratory, performed post-hoc on data collected primarily to validate the PKU-QOL.
METHODS: A multicentre, prospective, non-interventional, observational study conducted in France, Germany, Italy, The Netherlands, Spain, Turkey and the UK. Patients diagnosed with PKU aged ≥9 years old and treated with a Phe-restricted diet and/or Phe-free amino acid protein supplements and/or pharmacological therapy were included in the study; parents of at least one patient with PKU aged <18 years were also included. HRQoL was assessed by generic measures (Pediatric Quality-of-Life Inventory; Medical Outcome Survey 36 item Short Form; Child Health Questionnaire 28 item Parent Form) and the newly developed PKU-QOL. Mean generic domain scores were interpreted using published reference values from the general population. PKU-QOL domain scores were described overall and in different subgroups of patients defined according to severity of PKU, overall assessment of patient's health status by the investigator and treatment with tetrahydrobiopterin (BH4).
RESULTS: Data from 559 subjects were analysed: 306 patients (92 children, 110 adolescents, 104 adults) and 253 parents. Mean domain scores of generic measures in the study were comparable to the general population. The highest PKU-QOL impact scores (indicating greater impact) were for emotional impact of PKU, anxiety about blood Phe levels, guilt regarding poor adherence to dietary restrictions or Phe-free amino acid supplement intake and anxiety regarding blood Phe levels during pregnancy. Patients with mild/moderate PKU and those receiving BH4 reported lower practical and emotional impacts of the diet and Phe-free amino acid supplement intake.
CONCLUSION: Patients with PKU showed good HRQoL in the study, both with the generic and PKU-specific measures. Negative impacts of PKU on a patient's life, including the emotional impact of PKU and its management, was delineated by the PKU-QOLs across all age groups.

PMID: 26084935 [PubMed - indexed for MEDLINE]

[Bouveret syndrome: a case report and literature review].

Rozhl Chir. 2016;95(4):164-7

Authors: Kocián P, Bocková M, Schwarz J

Abstract
UNLABELLED: Bouveret syndrome is a gastric outlet obstruction caused by impaction of a gallstone that passes through a cholecystoduodenal or cholecystogastric fistula. It is a rare disease, most common in elderly women with multiple comorbidities and high surgical risk. The diagnosis can be made either radiologically or endoscopically. Endoscopic extraction is the preferred therapeutic option. Surgical intervention is indicated when endoscopic methods fail. We describe a case of Bouveret syndrome in a 79 years old woman. The report is followed by a review of literature on the diagnostics and treatment of this rare syndrome.
KEY WORDS: gallstones bilioenteric fistula gallstone ileus duodenal obstruction Bouveret syndrome.

PMID: 27226271 [PubMed - in process]

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol.

Syst Rev. 2016;5(1):89

Authors: Suen CM, Zhai A, Lalu MM, Welsh C, Levac BM, Fergusson D, McIntyre L, Stewart DJ

Abstract
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies.
METHODS: We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and individual study reporting will be assessed according to an itemized checklist based on the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines.
DISCUSSION: This systematic review will examine the efficacy and safety of regenerative cell therapy in preclinical models of PAH. As well, the literature will be assessed for study quality and risk of bias. The results will guide the design of future clinical trials and preclinical animal studies.
SYSTEMATIC REVIEW REGISTRATION: CAMARADES ( http://www.dcn.ed.ac.uk/camarades/SyRF/Protocols.htm ).

PMID: 27225668 [PubMed - in process]

Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net).

Orphanet J Rare Dis. 2016;11(1):69

Authors: Coler-Reilly AL, Yagishita N, Suzuki H, Sato T, Araya N, Inoue E, Takata A, Yamano Y

Abstract
BACKGROUND: At least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden.
METHODS: To learn more about this rare, debilitating disease, we established the national registration system "HAM-net" in March 2012. We continuously obtain detailed data from enrolled patients using the registration forms and an annual telephone interview. In this retrospective study, we describe the demographics and clinical histories of 383 registered patients from all over Japan.
RESULTS: Patients were diagnosed at a median of 53 years old, long after disease onset at 45. Most (55.3 %) were originally from the southernmost regions, Kyushu and Okinawa. The main initial symptoms were difficulty walking (81.9 %), urinary dysfunction (38.5 %), and lower limb sensory disturbances (13.9 %). Many patients reported frequent leg numbness and leg pain, and the vast majority required medical intervention for urinary symptoms and constipation. A median of 8 years elapsed from the onset of motor symptoms to Osame Motor Disability Score (OMDS) 5 (requiring unilateral support), 12.5 years to OMDS 6 (requiring bilateral support), and 18 years to OMDS 9 (unable to walk). Health Assessment Questionnaire - Disability Index (HAQ-DI) tasks related to mobility, as opposed to hand motions, were very difficult for HAM/TSP patients and well-correlated with OMDS. Scores on the MOS 36-Item Short-Form Health Survey (SF-36) indicated that physical functioning was severely impaired in HAM/TSP patients. Patients with a history of blood transfusion (19.1 %) were older and suffered from more severe disability as indicated by their high HAQ-DI scores. Patients with a family history of HAM/TSP (8.4 %) were younger and had relatively mild symptoms given their long disease durations; many (15.6 %) also had a relative with ATLL.
CONCLUSIONS: The HAM-net national registration system has been an effective tool for gathering personal and clinical data from HAM/TSP patients scattered throughout Japan. We expect to conduct many retrospective and prospective epidemiological studies using HAM-net in the future.

PMID: 27225443 [PubMed - in process]

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers.

Orphanet J Rare Dis. 2016;11(1):70

Authors: Morel T, Aymé S, Cassiman D, Simoens S, Morgan M, Vandebroek M

Abstract
BACKGROUND: Rare disease patients and caregivers face uncommon, serious, debilitating conditions often characterised by poor prognosis and limited treatment options. This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context.
METHODS: A mixed-methods survey with patients and caregivers was conducted in the United Kingdom across a range of rare diseases. Discrete-choice experiments that compared hypothetical treatment profiles of benefits and risks were used to measure respondent preferences across a set of seven attributes related to health outcomes, safety, and process of care. Bespoke questions on current disease management and the joint use of the 12-item WHODAS 2.0 questionnaire and of two Likert scales capturing self- and proxy-assessed disease-induced threat to life and impairment were implemented to describe disease context. Additionally, qualitative insights on the definitions of value and risk were collected from respondents.
RESULTS: Final study sample included 721 patients and 152 informal caregivers, across 52 rare diseases. When choosing between hypothetical novel treatments for rare diseases, respondents attributed most importance to drug response, risk of serious side effects, and the ability to conduct usual activities while on treatment. In contrast, attributes related to treatment modalities were the least important. Respondents expressed a willingness to accept risks in hopes of finding some benefit, such as a higher chance of drug response or greater health improvement potential. Increasing disease severity, impairment or disability, and the lack of effective therapeutic options were shown to raise significantly the willingness to gain benefit through increased risk.
CONCLUSIONS: This is the first study performing a quantitative discrete choice experiment amongst patients and caregivers across 52 rare conditions. It enables a more detailed understanding of the relationship between disease context, treatment attributes and the degree of risk respondents are willing to take to gain a specific degree of benefit. Researchers of novel therapeutics for rare diseases should be encouraged to invest in preference elicitation studies to generate rigorous patient evidence and specific regulatory guidance should be issued to acknowledge their importance and their use in marketing authorisations.

PMID: 27225337 [PubMed - in process]

Crowd Sourcing.

J Med Pract Manage. 2016 Jan-Feb;31(4):238-9

Authors: Baum N

Abstract
The Internet has contributed new words and slang to our daily vernacular. A few terms, such as tweeting, texting, sexting, blogging, and googling, have become common in most vocabularies and in many languages, and are now included in the dictionary. A new buzzword making the rounds in industry is crowd sourcing, which involves outsourcing an activity, task, or problem by sending it to people or groups outside a business or a practice. Crowd sourcing allows doctors and practices to tap the wisdom of many instead of relying only on the few members of their close-knit group. This article defines "crowd sourcing," offers examples, and explains how to get started with this approach that can increase your ability to finish a task or solve problems that you don't have the time or expertise to accomplish.

PMID: 27039640 [PubMed - indexed for MEDLINE]

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Ann Neurol. 2015 Dec;78(6):871-86

Authors: Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, Convers P, Maillart E, Guyant-Marechal L, Hannequin D, Fromager G, Afenjar A, Chantot-Bastaraud S, Valence S, Charles P, Berquin P, Rooryck C, Bouron J, Brice A, Lacombe D, Rossignol R, Stevanin G, Benard G, Burglen L, Durr A, Goizet C, Coupry I

Abstract
OBJECTIVE: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose function remains unknown, despite the description of numerous protein domains and the recent focus on its potential role in the regulation of mitochondrial physiology. This study aimed to identify new mutations in a large population of ataxic patients and to functionally analyze their cellular effects in the mitochondrial compartment.
METHODS: A total of 321 index patients with spastic ataxia selected from the SPATAX network were analyzed by direct sequencing of the SACS gene, and 156 patients from the ATAXIC project presenting with congenital ataxia were investigated either by targeted or whole exome sequencing. For functional analyses, primary cultures of fibroblasts were obtained from 11 patients carrying either mono- or biallelic variants, including 1 case harboring a large deletion encompassing the entire SACS gene.
RESULTS: We identified biallelic SACS variants in 33 patients from SPATAX, and in 5 nonprogressive ataxia patients from ATAXIC. Moreover, a drastic and recurrent alteration of the mitochondrial network was observed in 10 of the 11 patients tested.
INTERPRETATION: Our results permit extension of the clinical and mutational spectrum of ARSACS patients. Moreover, we suggest that the observed mitochondrial network anomalies could be used as a trait biomarker for the diagnosis of ARSACS when SACS molecular results are difficult to interpret (ie, missense variants and heterozygous truncating variant). Based on our findings, we propose new diagnostic definitions for ARSACS using clinical, genetic, and cellular criteria.

PMID: 26288984 [PubMed - indexed for MEDLINE]

Routine nail clipping leads to the diagnosis of amelanotic nail unit melanoma in a young construction worker.

J Cutan Pathol. 2015 Aug;42(8):505-9

Authors: Boni A, Chu EY, Rubin AI

PMID: 26272255 [PubMed - indexed for MEDLINE]

Noteworthy Professional News.

Adv Neonatal Care. 2015 Aug;15(4):235-6

Authors:

PMID: 26225589 [PubMed - indexed for MEDLINE]

Prenatal diagnosis of orbital melanotic neuroectodermal tumor in infancy.

Ultrasound Obstet Gynecol. 2015 Aug;46(2):249-50

Authors: Koob M, Fayard C, Pariente D, Adamsbaum C, Franchi-Abella S

PMID: 25594399 [PubMed - indexed for MEDLINE]