scholarly journals ABCD1 gene mutation in an Italian family with X-linkedadrenoleukodystrophy: case series

2021 ◽  
Vol 2021 ◽  
Author(s):  
Angelika Mohn ◽  
Nella Polidori ◽  
Chiara Aiello ◽  
Cristiano Rizzo ◽  
Cosimo Giannini ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Novel Mutation ◽  
Family Members ◽  
Case Series ◽  
Gene Mutations ◽  
Nutritional Intervention ◽  
Haematopoietic Stem Cell ◽  
List Type ◽  
Wide Range

Summary Adrenoleukodystrophy is a peroxisomal X-linked recessive disease caused by mutations in the ABCD1 gene, located on the X-chromosome (Xq28). Gene mutations in patient with adrenoleukodystrophy induce metabolic alterations characterized by impaired peroxisomal beta-oxidation and accumulation of very long chain fatty acid (VLCFA) in plasma and in all tissues. Although nutritional intervention associated with a various mixture of oil prevents the accumulation of VLCFA, to date no causal treatment is available. Therefore, haematopoietic stem cell transplantation (HSCT) and gene therapy are allowed only for very early stages of cerebral forms diagnosed during childhood.We reported a case series describing five family members affected by X-linked adrenoleukodystrophy caused by a novel mutation of the ABCD1 gene. Particularly, three brothers were affected while the sister and mother carried the mutation of the ABCD1 gene. In this family, the disease was diagnosed at different ages and with different clinical pictures highlighting the wide range of phenotypes related to this novel mutation. In addition, these characteristics stress the relevant role of early diagnosis to properly set a patient-based follow-up. Learning points We report a novel mutation in the ABCD1 gene documented in a family group associated to an X-ALD possible Addison only phenotype. All patients present just Addison disease but with different phenotypes despite the presence of the same mutations. Further follow-up is necessary to complete discuss the clinical development. The diagnosis of ALD needs to be included in the differential diagnosis in all patients with idiopathic PAI through accurate evaluation of VLCFA concentrations and genetic confirmation testing. Early diagnosis of neurological manifestation is important in order to refer timely to HSCT. Further follow-up of these family members is necessary to characterize the final phenotype associated with this new mutation.

scholarly journals A hereditaer nonpolyposus colorectalis carcinoma szindrómás betegek szűrésének és szoros utánkövetésének fontossága egy családfa bemutatása kapcsán

2017 ◽  
Vol 158 (30) ◽  
pp. 1182-1187
Author(s):  
Gergely Kóder ◽  
Judit Olasz ◽  
László Tóth ◽  
Hilda Urbancsek ◽  
Csilla András ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Family Members ◽  
Her Family ◽  
Mmr Genes ◽  
Gene Mutation Carrier ◽  
Hereditary Nonpolyposis ◽  
Dominant Disease ◽  
Associated Tumors

Abstract: Introduction: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. Aim: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. Materials and method: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. Results: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182–1187.

scholarly journals Cannabidiol as an add-on therapy to overcome the slow-onset and, possibly, resistance to antidepressant treatment: involvement of NAPE-PLD in the medial prefrontal cortex

2021 ◽  
Author(s):  
Franciele F. Scarante ◽  
Vinícius D. Lopes ◽  
Eduardo J. Fusse ◽  
Maria A. Vicente ◽  
Melissa R. Araújo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Rating Scales ◽  
Case Series ◽  
List Type ◽  
Stress Effect ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Wide Range ◽  
Resistant Depression

AbstractAntidepressants such as serotonin uptake inhibitors are the first-line pharmacological treatment for chronic stress-related psychiatric disorders. However, their late-onset therapeutic action and frequent side effects, however, are important challenges for clinicians and patients. Besides, around 30% of major depression patients are considered treatment-resistant. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid with a wide range of psychopharmacological effects, but its mechanism of action remains unclear. Here, we found that in male mice submitted to two different repeated stress protocols (chronic unpredictable and social defeat stress), low doses of CBD (7.5mg/Kg) caused an early-onset behavioral effect when combined to the antidepressant escitalopram (ESC-10mg/Kg). The behavioral effects of the ESC+CBD combination depended on the expression/activity of the N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD, responsible for synthesizing the endocannabinoid anandamide), but not the DAGLα, enzyme in the ventromedial prefrontal cortex. In addition, we described a case series with three treatment-resistant depression that were successfully treated with CBD as adjuvant therapy, as evaluated by standardized clinical rating scales. After 12 weeks of treatment, two patients were considered depression remitted (MADRS score lower than 10) while one patient successfully responded to CBD as add-on treatment (more than 50% decrease from the baseline MADRS). Our results suggest that CBD might be useful as an add-on therapy for optimizing the action of antidepressants. They also suggest that CBD’s beneficial actions depends on the facilitation of N-acylethanolamines actions in the medial prefrontal cortex.HighlightsIn mice, cannabidiol (CBD), but not escitalopram, induced a fast-onset anti-stress action.Combinations of sub-effective doses of CBD and escitalopram produce anti-stress effects after only 7 days.The Escitalopram + CBD treatment modulated synaptic protein markers in the medial prefrontal cortex.CRISPR-Cas9-mediated knockdown of NAPE-PLD in the medial PFC prevents the anti-stress effect of the Escitalopram + CBD.Adding CBD to an antidepressants regimen successfully treated three patients with treatment resistant depression.Graphical abstract

A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

2020 ◽  
Author(s):  
Haydar Bağış ◽  
Özden Öztürk ◽  
Semih Bolu ◽  
Bayram Taşkın
Keyword(s):  
Novel Mutation ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
The Other ◽  
Cornelia De Lange Syndrome ◽  
Other Hand ◽  
Wide Range ◽  
Cornelia De Lange

AbstractThe Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Temporal Bone Fractures Caused by Ballistic Projectiles: A Systematic Review

2020 ◽  
pp. 019459982096879
Author(s):  
Kenneth L. Kennedy ◽  
Elizabeth Cash ◽  
Jessica Petrey ◽  
Jerry W. Lin
Keyword(s):  
Temporal Bone ◽  
Bone Fractures ◽  
Case Reports ◽  
Case Series ◽  
Gunshot Wounds ◽  
Individual Case ◽  
Future Research ◽  
Wide Range ◽  
Intracranial Complications

Objective Ballistic injuries to the temporal bone are uncommon but devastating injuries that damage critical neurovascular structures. This review describes outcomes after ballistic injuries to the temporal bone and offers initiatives for standardized high-quality future research. Data Sources A systematic search of PubMed, Embase, and Cochrane. Review Methods Studies in the review included adults who experienced temporal bone fractures due to gunshot wounds and survived longer than 48 hours. Individual case reports were excluded. The various searches returned 139 results, of which 6 met inclusion criteria. Results Most of the included studies are case series with low-level evidence that report a wide range of outcomes and follow-up. Outcomes include demographic patient information, audiologic outcomes, vascular injuries, intracranial complications, facial nerve function, and surgical indications. Conclusion This review is the first to characterize the nature and progression of patients who experienced gunshot wounds to the temporal bone. Although all patients share an etiology of injury, they often have vastly different hospital courses and outcomes. This review provides a basis for future studies to guide care for these injuries, as most of the existing literature includes small dated case series.

Rare Cause of Infantile Hypercalcemia: A Novel Mutation in the SLC34A1 Gene

2018 ◽  
Vol 91 (4) ◽  
pp. 278-284 ◽  
Author(s):  
Erdal Kurnaz ◽  
Şenay Savaş Erdeve ◽  
Semra Çetinkaya ◽  
Zehra Aycan
Keyword(s):  
Metabolic Alkalosis ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Phosphate Homeostasis ◽  
Clinical Syndromes ◽  
Wide Range ◽  
Medullary Nephrocalcinosis ◽  
Proximal Tubular ◽  
Idiopathic Infantile Hypercalcemia ◽  
Sodium Replacement

Background: Under physiological conditions, proximal tubular phosphate reabsorption via NaPi-IIa (and NaPi-IIc) ensures the maintenance of phosphate homeostasis. Impairment of NaPi-IIa, encoded by SLC34A1, is associated with various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi’s syndrome with chronic kidney disease, and idiopathic infantile hypercalcemia and nephrocalcinosis. Methods: A patient was referred to our hospital due to hyponatremia, hyperkalemia, and hypophosphatemia, as well as persistent hypercalcemia after fluid therapy and sodium replacement. At admission to our hospital, potassium and sodium values were normal. After initiation of phosphorus therapy, hypokalemia and metabolic alkalosis were observed. Renal sonography showed bilateral medullary nephrocalcinosis. Analyses of the SLC34A1 gene were performed due to hypercalcemia and hypophosphatemia. Results: Gene analyses identified a novel homozygous c.682T>C (p.W228R) (p.Trp228Arg) mutation. There are no previous reports of patients with SLC34A1 gene mutations presenting with hypokalemia and metabolic alkalosis. Conclusion: Herein, we present a case of infantile hypercalcemia 2 with a very different phenotype from that of previously described patients. Our findings provide further evidence for the wide range of phenotypic heterogeneity associated with NaPi-IIa impairment.

Simultaneous cochlear implantation and removal of acoustic neuroma: implications for hearing

2020 ◽  
Vol 134 (6) ◽  
pp. 519-525
Author(s):  
S Roberts ◽  
B Levin ◽  
H Sanli ◽  
R Ferch ◽  
K Kong ◽  
...  
Keyword(s):  
Acoustic Neuroma ◽  
Cochlear Implantation ◽  
Case Series ◽  
Auditory Brainstem ◽  
Tertiary Referral Centre ◽  
Clinical Scenarios ◽  
Facial Nerve Monitoring ◽  
Wide Range ◽  
Brainstem Response

AbstractObjectiveTo present our data evaluating the feasibility of simultaneous cochlear implantation with resection of acoustic neuroma.MethodsThis paper describes a case series of eight adult patients with a radiologically suspected acoustic neuroma, treated at a tertiary referral centre in Newcastle, Australia, between 2012 and 2015. Patients underwent cochlear implantation concurrently with removal of an acoustic neuroma. The approach was translabyrinthine, with facial nerve monitoring and electrically evoked auditory brainstem response testing. Standard post-implant rehabilitation was employed, with three and six months’ follow-up data collected. The main outcome measures were: hearing, subjective benefit of implant, operative complications and tumour recurrence.ResultsEight patients underwent simultaneous cochlear implantation with resection of acoustic neuroma over a 3-year period, and had 25–63 months’ follow up. There were no major complications. All patients except one gained usable hearing and were daily implant users.ConclusionSimultaneous cochlear implantation with resection of acoustic neuroma has been shown to be a safe treatment option, which will be applicable in a wide range of clinical scenarios as the indications for cochlear implantation continue to expand.

scholarly journals Predictors of adverse outcome in patients with suspected COVID-19 managed in a ‘virtual hospital’ setting: a cohort study

2020 ◽  
Author(s):  
Nick A Francis ◽  
Beth Stuart ◽  
Matthew Knight ◽  
Rama Vancheeswaran ◽  
Charles Oliver ◽  
...  
Keyword(s):  
Mental Health ◽  
Mental Health Problems ◽  
Adverse Outcome ◽  
Hospital Setting ◽  
Health Problems ◽  
List Type ◽  
Increased Risk ◽  
Wide Range ◽  
History Of

ABSTRACTObjectiveIdentify predictors of adverse outcome in a Virtual Hospital (VH) setting for COVID 19.DesignReal-world prospective observational study.SettingVirtual hospital remote assessment service in West Hertfordshire NHS Trust, UK.ParticipantsPatients with suspected COVID-19 illness enrolled directly from the community (post-accident and emergency (A&E) or medical intake assessment) or post-inpatient admission.Main outcome measureDeath or (re-)admission to inpatient hospital care over 28 days.Results900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 post-inpatient) were included in the analysis. 76 (8.4%) of these experienced an adverse outcome (15 deaths in admitted patients, 3 deaths in patients not admitted, and 58 additional inpatient admissions). Predictors of adverse outcome were increase in age (OR 1.04 [95%CI: 1.02, 1.06] per year of age), history of cancer (OR 2.87 [95%CI: 1.41, 5.82]), history of mental health problems (OR 1.76 [95%CI: 1.02, 3.04]), severely impaired renal function (OR for eGFR <30 = 9.09 [95%CI: 2.01, 41.09]) and having a positive SARS-CoV-2 PCR result (OR 2.0 [95% CI: 1.11, 3.60]).ConclusionsThese predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to identify the reasons for increased risk of adverse outcome associated with cancer and mental health problems.ARTICLE SUMMARYStrengths and limitations of this studyThe study uses anonymised data from all patients registered for the virtual hospital between 17/03/20 and 17/05/20, and therefore selection bias is not an issue.At the time of this study, this was the only service providing remote follow-up for patients with suspected COVID-19 in the area, and therefore our findings are likely to be relevant to primary care patients receiving remote follow-up.We were able to collect reliable data on a wide range of clinical and demographic features, and reliably follow all patients for the primary outcome for at least two weeks following their discharge from the VH.We were not able to extract detailed symptom or clinical examination data, and there were significant amounts of missing data for some variables.Our study is likely underpowered to detect all predictors, especially in the analysis of our two sub-groups

scholarly journals Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations*

Amyloid ◽  
2019 ◽  
Vol 26 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Isabel Conceição ◽  
Thibaud Damy ◽  
Manuel Romero ◽  
Lucía Galán ◽  
Shahram Attarian ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Gene Mutations ◽  
Attr Amyloidosis
Sign in / Sign up

Export Citation Format

Share Document