Syndrome Type Research Articles

Targeting the IKs Channel PKA Phosphorylation Axis to Restore Its Function in High-Risk LQT1 Variants.

The KCNQ1+KCNE1 (IKs) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the IKs channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between IKs channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear. Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/IKs channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions. By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of IKs channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of IKs. We refer to this pattern as the IKs channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the IKs channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities. Our findings not only elucidate the molecular mechanism of PKA-dependent IKs channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants.

To biopsy or not to biopsy a teenager with typical idiopathic nephrotic syndrome? Start steroids first.

It is well known that minimal change disease (MCD) and focal segmental glomerulosclerosis are the most common histopathology findings in children with idiopathic nephrotic syndrome. Moreover, several studies demonstrated that MCD is associated with high steroid-responsiveness and a low incidence of kidney failure, suggesting that routine kidney biopsy is not warranted. Over time, the indications for performing a kidney biopsy have become increasingly stringent, aiming to limit unnecessary invasive procedures in the paediatric population. The most recent guidelines state that a kidney biopsy is not usually necessary at disease onset. Still, it should be performed in case of atypical features suggestive of systemic diseases or glomerulonephritis and in case of steroid-resistance, to assess the different differential diagnoses, regardless of patient age. Moreover, it has been shown that the best prognostic marker in childhood nephrotic syndrome is response to treatment and that kidney histology is not accurate in predicting prognosis. Furthermore, a kidney biopsy is not necessary to predict the relapsing course. Notably, kidney biopsy is an invasive procedure and may lead to significant complications. Finally, novel non-invasive biomarkers have been validated or are in the process of being approved to guide differential diagnoses and thus limit the need for kidney biopsies in patients with typical nephrotic syndrome. In the following sections, we aim to explain why initiating steroid treatment as the initial approach in teenagers with typical nephrotic syndrome is a reasonable strategy. Additionally, we explore how kidney biopsy indications may be alleviated in this population.

Incidence of Tethered Cord Syndrome in Pediatric Patients With Neurofibromatosis Type 1

ObjectiveThe link between Tethered Cord Syndrome (TCS) and Neurofibromatosis Type 1 (NF1) remains unclear. To date, only two studies have indicated a high occurrence of TCS in the pediatric NF1 patient population. Our study aims to ascertain the incidence of TCS among Chinese pediatric patients with NF1. MethodsA single-institution, 8-year retrospective analysis at a tertiary-level children's hospital was conducted for patients with NF1 who underwent surgery for TCS. The clinical features, imaging characteristics, genetic testing outcomes, and histopathological findings of pediatric NF1 patients with TCS were analyzed. ResultsDuring the study period, a total of 115 pediatric patients were diagnosed with NF1. Among these 115 NF1 patients, 11 individuals, accounting for 9.6% of the sample, were confirmed to have TCS. This rate of occurrence is significantly higher than the incidence rate of TCS in the general population, which stands at 0.17%. All 11 of the pediatric NF1 patients underwent surgery for TCS. Out of the 11 patients who were advised to have tethered cord release surgery, 4 (which is 36.4%) were girls, and the average age of these 11 patients was 8.6 years old, with ages ranging from 2 to 17 years old. The conus medullaris position of the 11 pediatric NF1 patients ranged from L1 to L2, and 10 of them (91%) had a filum terminale lipoma, characterized by high signal intensity on T1-weighted magnetic resonance (MR) images. Another patient was diagnosed with Occult Tethered Cord Syndrome (OTCS). All 11 pediatric NF1 patients exhibited symptoms associated with TCS, such as neuromotor dysfunction, abnormalities in urination, defecation, skeletal system abnormalities, or pain. Eight of the 11 pediatric NF1 patients had undergone genetic testing, which is a crucial part of the diagnostic process for NF1. The histopathological examination of the 11 pediatric NF1 patients who underwent surgery revealed that 10 patients had fatty infiltration of the filum terminale (FT), while the remaining patient exhibited fibrosis of the filum terminale (FT). ConclusionsIn the group of pediatric patients with NF1, the incidence of TCS, presenting to the pediatric neurosurgery clinic for any reason, is significantly higher than that of the general population. However, the pathophysiological relationship between NF1 and TCS is still not clear. It is essential to provide counseling to NF1 patients and their families about the symptoms of TCS to make sure they are aware and can seek the necessary care when needed. This underscores the importance of not only diagnosing NF1 but also staying alert for related conditions like TCS, which may have a higher occurrence in this demographic.

SLC12A1 variant c.1684+1 G>A causes Bartter syndrome type 1 by promoting exon 13 skipping.

Bartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss-of-function variants in the SLC12A1 gene. It is characterized by metabolic alkalosis and prenatal-onset polyuria leading to polyhydramnios. We identified pathogenic gene in a 12-day-old newborn boy with Bartter syndrome type 1 using whole-exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre-mRNA splicing. We found a compound heterozygous variants in the SLC12A1 gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G>A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G>A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G>A abolished a consensus splice donor site of SLC12A1 intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of SLC12A1 function. Using a cell-based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant SLC12A1 c.1684+1 G>A on pre-mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.

Swimming performance, but not metabolism, is related to a boldness-activity syndrome in schoolmaster snapper (Lutjanus apodus).

Commercial overexploitation and climate change can alter the physiology and behavior of marine organisms, although intraspecific phenotypic responses to such changes can vary greatly depending on the environment, species, and severity of the stressor. Under the pace-of-life syndrome (POLS) hypothesis, behavior, physiology, and life-history traits are linked, and thus, affected by selection targeting any aspect of organismal biology. However, these links are understudied in tropical marine fishes, and further work is needed to better understand the impacts of fisheries and climate change on wild stocks. Moreover, tropical regions have a greater reliance on fisheries; thus investigations should focus on species with substantial socioeconomic value to ensure benefits at the local level. This study aimed to address this need by measuring the behavior (boldness and activity), metabolism, and swimming performance (using a critical swim speed [Ucrit] test) of schoolmaster snapper Lutjanus apodus in Eleuthera, the Bahamas. We report a strong positive correlation between boldness and activity, high repeatability of these behavioral metrics, and two groupings that were consistent with "proactive" and "reactive" behavioral types. These behavioral types differed significantly in their swimming performance, with reactive individuals having a 13.1% higher mean Ucrit. In contrast, no significant differences were found in the measured metabolic parameters between behavioral types. This study is the first to investigate the intraspecific links between behavior and physiology in a snapper species, using the novel and ecologically relevant comparison of Ucrit with behavioral syndrome types. These data suggest that additional research is needed to better predict the success of proactive/reactive tropical fish if overexploited and as influenced by climate change.

Efficacy and safety of neridronate in paediatric type I complex regional pain syndrome: a multicentre experience.

Evidence regarding the efficacy of neridronate in the treatment of complex regional pain syndrome type I (CRPS I) is increasing, however, very little data are available in paediatric age. Our aim was to analyse the safety and the efficacy of neridronate in a case series of children with CRPS I, according to the Budapest criteria, who did not respond to previous pharmacological and physical therapy. We collected data of children affected by CRPS I from three paediatric rheumatology centres who received neridronate. Efficacy was evaluated by changes in pain intensity, vasomotor changes, physical function, need for pain medications and MRI findings. Adverse effects were also documented. Five children (3 females and 2 males, mean age 10.4 years, range 7-13 years) who received neridronate (4 intravenous, 1 intramuscular) were included. All patients had failed previous medical treatments (NSAIDs in 4, local steroids in 2, gabapentin, vitamin D and calcium supplementation in 1) and non-medical therapies (physiotherapy in 4, magnetotherapy in 2, laser in 1). Four out of five patients reported a significant improvement in pain (average VAS pre-treatment 9.6, post-treatment 2.6), recovery of physical function, and a reduced need for pain medications. Before treatment, all patients underwent MRI which revealed bone oedema that disappeared in the three of them after treatment. Neridronate was well-tolerated as only one patient experienced mild flu-like symptoms. Our data suggest that in children as in adults with CRPS I, neridronate may represent an effective and safe treatment option, particularly in those who do not respond to other pain treatments.

TRPS1, a sensitive marker for different histological and molecular types of breast cancer

ObjectivesWe explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC).MethodsTRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types.ResultsA total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p < .001). TRPS1 showed a higher positive rate (93.13%) in TNBC compared to GATA binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP-15) and forkhead box transcription Factor C 1 (FOXC1).ConclusionsIn conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Acute effect of gold nanoparticles on neuropathic pain in a model of regional complex pain syndrome

We evaluated the effects of gold nanoparticles (AuNPs) administered in the acute phase of an animal model of Complex Regional Pain Syndrome Type I (CRPS-I). Oxidative stress parameters [substances reactive to thiobarbituric acid (TBA-RS), total sulfhydryl content (SH), protein carbonyl content and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] and pain, through mechanical and thermal allodynia, were evaluated in the blood and sciatic nerves of mice. Animals were anesthetized and an elastic tourniquet was used around the left hind paw for 120 minutes, followed by measurements of the mechanical threshold and thermal. Animals received intraperitoneal administrations of AuNPs at concentrations of 2.5 mg/L, 7.0 mg/L and 22.0 mg/L, Ankyrin Transient Potential Receptor 1 (TRPA1) antagonist (HC030031) or saline vehicle after induction of CRPS-I. AuNPs showed significant results in thermal and mechanical anti-allodynic effects on day 1 (2.5 mg/L), days 2 and 3 (7.0 and 22.0 mg/L). The TRPA1 reduced mechanical allodynia (days 1 and 2) and thermal allodynia (days 1, 2 and 3), in addition to reversing the changes caused by CRPS-I in oxidative stress. The CRPS-I model increased TBA-RS, reduced the total sulfhydryl content and increased CAT activity. The results showed that, at all concentrations, AuNPs reversed the increase in CAT. At 7.0 mg/L partially reversed and at 22.0 mg/L completely reversed the increase in TBA-RS levels and at 22.0 mg/L reversed the reduction in sulfhydryl content.

Evaluating current acute aortic syndrome pathways: Collaborative Acute Aortic Syndrome Project (CAASP)

Abstract Background Diagnosis of acute aortic syndrome is challenging and associated with high perihospital mortality rates. The study aim was to evaluate current pathways and understand the chronology of acute aortic syndrome patient care. Method Consecutive patients with acute aortic syndrome imaging diagnosis between 1 January 2018 and 1 June 2021 were identified using a predetermined search strategy and followed up for 6 months through retrospective case note review. The UK National Interventional Radiology Trainee Research and Vascular and Endovascular Research Network co-ordinated the study. Results From 15 UK sites, 620 patients were enrolled. The median age was 67 (range 25–98) years, 62.0% were male and 92.9% Caucasian. Type-A dissection (41.8%) was most common, followed by type-B (34.5%); 41.2% had complicated acute aortic syndrome. Mode of presentation included emergency ambulance (80.2%), self-presentation (16.2%), and primary care referral (3.6%). Time (median (i.q.r.)) to hospital presentation was 3.1 (1.8–8.6) h and decreased by sudden onset chest pain but increased with migratory pain or hypertension. Time from hospital presentation to imaging diagnosis was 3.2 (1.3–6.5) h and increased by family history of aortic disease and decreased by concurrent ischaemic limb. Time from diagnosis to treatment was 2 (1.0–4.3) h with interhospital transfer causing delay. Management included conservative (60.2%), open surgery (32.2%), endovascular (4.8%), hybrid (1.4%) and palliative (1.4%). Factors associated with a higher mortality rate at 30 days and 6 months were acute aortic syndrome type, complicated disease, no critical care admission and age more than 70 years (P &amp;lt; 0.05). Conclusions This study presents a longitudinal data set linking time-based delays to diagnosis and treatment with clinical outcomes. It can be used to prioritize research strategies to streamline patient care.

Popliteal Artery Entrapment Syndrome: Updates for Evaluation, Diagnosis, and Treatment.

Popliteal artery entrapment syndrome remains difficult to diagnose. Meanwhile, our limited knowledge and understanding make treatment decisions complex. The list of differential diagnoses for exertional leg pain is broad. Oftentimes, patients exhibit confounding and coexisting diagnoses. However, accurate and rapid diagnosis of popliteal artery entrapment syndrome is essential to reduce potential lasting damage to the popliteal artery. A combination of clinical history, physical examination, ankle-brachial index, along with dynamic and static imaging such as duplex ultrasound, computed tomography angiogram, and magnetic resonance angiography, aids diagnosis. Surgical treatment may be definitive depending on the type of popliteal artery entrapment syndrome, but there have been recent advances in diagnostics with intravascular ultrasound and nonsurgical treatment with botulinum toxin type A. Further research is needed to standardize diagnostic criteria, uncover innovative diagnostic methods, and validate promising nonoperative treatment options.

Predictors of quality of life (QOL) and treatment adherence among children with nephrotic syndrome.

Any significant changes in the growth and development of any aspect of life will ultimately affect the health-related quality of life (HRQOL) of children with nephrotic syndrome. Various factors can influence treatment adherence, which can promote or decline the child's quality of life (QOL). Objective: To assess the quality of life and adherence to treatment regimen and to identify the predictors of QOL and adherence to treatment regimen among children with nephrotic syndrome. A cross-sectional study was conducted among 59 children with nephrotic syndrome who attended the Paediatric Department of AIIMS, Bhubaneswar, using the PedsQL 4.0 generic core scale to assess the quality of life and adherence response scale. Both descriptive and inferential statistics were performed using the SPSS 20 version. The overall QOL median score was 93.48, with an IQR of 18.48, which indicated good QOL. A median score of treatment adherence was 16 with IQR 5, which indicated that the overall treatment adherence was good. Type of nephrotic syndrome (P = 0.014), developmental stage (P = 0.018), education of mother (P = 0.026), and occupation of mother (P = 0.026) were the variables predicted QOL. Duration of disease (P = 0.006) and duration of therapy (P = 0.005) significantly predicted treatment adherence. Children need continuous reinforcement on treatment adherence strategies to attain and maintain good QOL so that it can help to reduce the disease severity. Controlling the predictors that influence the QOL and treatment adherence has to be counseled among the parents so that their adherence can be sustained throughout the disease process to maintain good QOL.

Clinical and Angiographic Profile of Non-ST Elevation Myocardial Infarction Patients with Multivessel Disease: A Study in a Tertiary Care Hospital in Bangladesh

Background: Non-ST elevation myocardial infarction (NSTEMI) is a type of acute coronary syndrome without ST-segment elevation on electrocardiography. Many non-ST elevation myocardial infarction patients have multivessel disease, which leads to worse outcomes compared to single-vessel disease. Their clinical and angiographic profiles provide valuable insightf into the nature, severity, and treatment of this common cardiac condition. This study aimed to evaluate the clinical and angiographic profiles of non-ST elevation myocardial infarction patients with multivessel disease. Methods: This prospective study was conducted in the Department of Cardiology, National Heart Foundation Hospital and Research Institute, Dhaka, Bangladesh from September 2022 to August 2023. The study enrolled 270 consecutive patients with NSTEMI. Coronary angiography and electrocardiogram were used in assessing the disease condition. The data were analyzed using SPSS version 23.0. Results: The mean age of total participants was 54.31 ±10.54 years and most of them were male (77.8%). Majority of the patients had hypertension (68.1%), diabetes mellitus (59.3%), and dyslipidemia (58.5%). In the clinical assessment, 89.6% of patients had femoral access, 31.1% had a bifurcation lesion, 8.1% showed calcification, and 22.6% had a left main lesion. Stents were used in 41.9% of cases, with a mean total stent length of 55.8 ±26.9 mm. The mean left ventricular ejection fraction was 49.10 ±7.3%. Among the major culprit vessel involvements identified, 6% involved the left main (LM) artery, 56% involved the left anterior descending (LAD) artery, 34% involved the left circumflex (LCX) artery, and 39% involved the right coronary artery (RCA). Regarding the final angiographic findings among the total participants, double vessel disease (DVD) was observed in 40% of cases, while triple vessel disease was observed in 60% of cases. Conclusion: The increased prevalence of triple vessel disease among non-ST elevation myocardial infarction patients underscores the importance of heightened vigilance among healthcare providers and policymakers. Understanding the clinical and angiographic profiles of these patients is essential for effective management strategies.

Low foetal heart rate, a potentially ominous finding: case report

Abstract Background Congenital long QT syndrome (LQTS) type 1 is characterized by abnormally prolonged ventricular repolarization caused by inherited defects in cardiac potassium channels. Patients are predisposed to ventricular arrhythmias and even sudden cardiac death. In some cases, foetal sinus bradycardia is the only sign, making prenatal diagnosis challenging. Physicians should be aware of this subtle presentation of LQTS. Early diagnosis and proactive treatment are crucial for preventing unexpected cardiac events. Case summary A healthy and asymptomatic 25-year-old pregnant woman was referred to our institute for cardiac evaluation after persistent foetal sinus bradycardia was detected during repeated ultrasounds, despite the absence of any foetal morphological or functional cardiac anomalies. After a thorough assessment, the mother was diagnosed with LQTS type 1, as confirmed by molecular genetic testing. Appropriate management, including maternal medication and increased surveillance, was initiated. The infant was delivered safely, and his electrocardiogram revealed a significantly prolonged QTc interval. Genetic testing confirmed the maternally inherited variant in KCNQ1 gene, and beta-blocker therapy was started. No arrhythmic events were noted. Discussion Detection and careful stratification of foetal heart rate (FHR) is crucial in every pregnancy. Foetal bradycardia can be caused by both maternal and foetal factors. Persistent low FHR should raise a high suspicion for LQTS. The condition may also present with atrioventricular blocks, torsades de pointes, or sudden intrauterine foetal demise. Accurate and early diagnosis of LQTS is essential for implementing appropriate management strategies, which include vigilant monitoring, effective medical treatment, careful planning of delivery, and post-natal care.

Further characteristics of Noonan Syndrome type 13 caused by MAPK1 loss of function variant: Case report and literature review

Further characteristics of Noonan Syndrome type 13 caused by MAPK1 loss of function variant: Case report and literature review

Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a RAD21 Variant.

Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole-exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. A 13.3-year-old male patient with a height of 136.5 cm (-3.5 SDS) and a weight of 28.4 kg (-3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.

Polyglandular Syndrome type III in a young patient: case report

Introduction: Autoimmune polyglandular syndromes (APS) are rare diseases defined by the coexistence of at least two autoimmune endocrine diseases. Objective: To describe a case of type III polyglandular syndrome in a young patient. Case report: Female, 37 years old, with hypothyroidism, presented with a weight loss of 9 kg, daily vomiting, asthenia, fatigue, and postprandial fullness for 3 months. He also reported arthritis in his wrists, shoulders, and hips. In laboratory tests, macrocytic and hyperchromic anemia associated with leukopenia, as well as hypovitaminosis B12, was observed. Pernicious anemia was investigated as the cause of this deficiency. Upper digestive endoscopy showed moderate gastritis – histopathological with gastric atrophy, positive anti-intrinsic factor antibody. Due to inflammatory arthralgia, ANA was requested, with an associated positive anti-dsDNA result of 1:80. In the EULAR/2019 diagnostic criteria for Systemic Lupus Erythematosus (SLE), she presented 14 points, thus she was diagnosed with SLE, and hydroxychloroquine (HXC) was started. Conclusion: SPA is rare, mainly in association with non-glandular autoimmunity, following an early diagnosis.

Complexity and multimorbidity in autoimmune polyendocrine syndrome type 2 - a case report

Complexity and multimorbidity in autoimmune polyendocrine syndrome type 2 - a case report

Management Targeted Genetic Evaluation of an Idiopathic Neuropathy Cohort Through ATTRv Amyloidosis Screening.

While the reported prevalence of polyneuropathies is 1%-3%, the incidence of hereditary transthyretin amyloidosis in the United States is estimated to be 1 in 100 000 individuals. Polyneuropathies are known to be difficult to treat and lead to significant morbidity. The aim of pain management is symptomatic treatment, with varying approaches to progression prevention being based on the causative pathophysiology.We assessed the prevalence of hereditary amyloid transthyretin variant (ATTRv) amyloidosis, a progressive autosomal dominant multisystem disease caused by the abnormal formation and extracellular deposition of transthyretin protein fibrils in various tissues, in an idiopathic polyneuropathy population by using genetic analysis. Individuals aged 18 and over with an established diagnosis of polyneuropathy, via electromyography testing that was deemed to be idiopathic, at a large, urban neurology clinic consented to an institutional review board-approved protocol for genetic testing. No further exclusions were made regarding age of onset, family history, axonal neuropathy subtype, comorbidities suggestive of ATTRv amyloidosis, etc. Clinical genetic testing was performed on 134 participants via an 81-gene panel associated with inherited neuromuscular disorders or targeted TTR gene sequencing with deletion and duplication analysis. Within our cohort, 38.06% had at least one reportable finding in one of 38 distinct genes, for a total of 76 reported alterations. Four individuals were identified as having a single pathogenic alteration in an autosomal recessive gene, consistent with carrier status for the 4 following disorders: congenital insensitivity to pain with anhidrosis (NTRK1), Charcot-Marie-Tooth disease type IIP (LRSAM1), Brown-Vialetto-Van Laere syndrome type II (SLC52A2), hereditary sensory and autonomic neuropathy type III (IKBKAP). One individual was found to have a variant of uncertain significance (VUS) (p.G103D) in the TTR gene. Precision medicine on the molecular level with genetic testing in the identification of specific neuropathies may provide clinicians with more detailed information for developing a more direct therapeutic and treatment modality for better-targeted management. Further investigation is needed to expand on the knowledge and understanding of the clinical relevance surrounding the alterations found in the genetic evaluation of idiopathic neuropathy.

High-sensitivity QCM humidity sensor based on chitosan/carboxymethylated multiwalled carbon nanotubes composite for non-contact respiratory monitoring

Respiratory humidity is an important indicator that can reflect respiratory disorders and is easily accessible in daily life, thus attracting attention in non-contact home respiratory monitoring systems. In this work, a high-sensitivity quartz crystal microbalance (QCM) humidity sensor based on a chitosan/carboxymethylated multiwalled carbon nanotubes composite coating is developed with a response time of 36 s and a recovery time of 38 s. The humidity variations from 11 to 97 % can be detected while the wet hysteresis is 0.95 % RH. The sensor also exhibits good repeatability and stability. The physicochemical characterizations of the materials reveal the mechanism of the rapid humidity response, i.e., compared to the physically blended CS with MWCNT, the crosslinking CS-MWCNT formed the new intercalation by stronger hydrogen and amide bonding, which leads to the homogeneous coverage of CS on MWCNT, exposing more active sites and facilitating the binding rate of water molecules. Combined with respiration monitoring, the sensor is able to accurately monitor human respiration rate and depth in real time, effectively predicting and differentiating between different types of obstructive sleep apnea syndromes, providing a fast and reliable solution for daily health monitoring.

Expanding the genetic landscape of Usher syndrome type IV caused by pathogenic ARSG variants.

Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes. Among the ultra-rare and recently discovered genes is ARSG, coding for the lysosomal sulfatase Arylsulfatase G. This subtype was assigned as "USH IV" with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement. Here, we describe nine new subjects and the clinical description of four cases with the USH IV phenotype bearing seven novel and two known pathogenic variants. Functional experiments indicated the complete loss of sulfatase enzymatic activity upon ectopic expression of mutated ARSG cDNA. Interestingly, we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis. Our study expands the genetic landscape of ARSG-USH IV and the number of known subjects by more than 30%. These findings highlight that USH IV likely has been underdiagnosed and emphasize the need to test molecularly unresolved subjects with deafblindness syndrome. Finally, testing of ARSG should be considered for the genetic work-up of apparent isolated inherited retinal diseases.