Case Of GS Research Articles

Primary Intraoral Granulocytic Sarcoma: A Case Report and Review of Literature

AbstractGranulocytic sarcoma (GS) is a rare extramedullary malignant tumor composed of immature granulocytes, including myeloblasts, promyelocytes, and myelocytes. In most cases, these are associated with persisting blood dyscrasias such as acute myeloid leukemia and chronic myeloid leukemia. To date, 32 cases of GS involving orofacial region have been reported in the English literature. Out of these, only a few presented without any systemic complications. This case reports an unusual occurrence of GS without any associated leukemia involving the mandible of a 29-year-old male patient. Hematoxylin and eosin–stained sections revealed the presence of numerous rounds to ovoid myeloblasts with a multilobated, vesicular nucleus and a prominent nucleolus. The cells stained positive for Cluster of Differentiation 68, lysozyme, and myeloperoxidase. He later underwent chemotherapy but succumbed in the interim period of chemotherapy. We hereby report a unique case of GS of mandible in an apparently healthy individual who deteriorated rapidly; an early and accurate diagnosis of which could have been life-saving.

Intraoperative Ultrasonography for the Surgical Treatment of Grisel Syndrome of the Adult: Management of A Rare Condition.

This is a narrative review and case report. To review the literature concerning Grisel syndrome physiopathology, diagnosis, and surgical reports, highlighting the decision-making for treatment and its timing. We describe the role of intraoperative US in the management of 2 cases of GS of the adult. GS is a rare nontraumatic post inflammatory C1-C2 rotatory instability usually affecting children; adult cases are even rarer, and the role of surgical treatment is not well defined. Case 1: A 72-year-old man with upper cervical pain and no neurological deficit; radiologic examination revealed C1-C2 spondylitis and epidural abscess. After antibiotic therapy, the patient developed cervical instability. Hence, surgical decompression and C1-C2 stabilization were performed. Case 2: An 82-year-old woman with progressive right hemiparesis. CT and MRI showed C1-C2 spondylitis with retro-odontoid epidural abscess. Atlanto-axial rotatory instability was evident so surgery was achieved. In both cases, intraoperative US was useful for localizing retro-odontoid abscess and allowing safe puncture of the collection, leading to its remarkable radiologic reduction. GS in adults remains a challenge: Patients should be closely monitored concerning neurological and inflammatory status. We describe the successful use of intraoperative US for draining retro-odontoid abscess for the first time, with satisfactory postoperative outcome without need of circumferential approach.

X-Ray Polarimetry as a Tool to Constrain Orbital Parameters in X-Ray Binaries

X-ray binary systems consist of a companion star and a compact object in close orbit. Thanks to their copious X-ray emission, these objects have been studied in detail using X-ray spectroscopy and timing. The inclination of these systems is a major uncertainty in the determination of the mass of the compact object using optical spectroscopic methods. In this paper, we present a new method to constrain the inclination of X-ray binaries, which is based on the modeling of the polarization of X-rays photons produced by a compact source and scattered off the companion star. We describe our method and explore the potential of this technique in the specific case of the low-mass X-ray binary GS 1826−238 observed by the Imaging X-ray Polarimetry Explorer observatory.

A case of Gitelman syndrome with homozygous SLC12A3 deletion presenting with epilepsy

BackgroundGitelman syndrome (GS) is a rare autosomal recessive hereditary renal tubular disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria.Case presentationWe report a rare case of GS with homozygous loss of SLC12A3 presenting with epilepsy. The patient was a 21-year-old female who sought medical attention for seizures. Her condition primarily manifested as epilepsy, diarrhea, and weakness of limbs. Through genetic analysis, we confirmed the diagnosis of this case and formulated a comprehensive approach for its management.ConclusionsThis case report extends the clinical symptoms of GS and provides a complete family of GS as a reference for subsequent studies.

Comparison of Outcomes in Below-Knee Amputation Between Vascular, General, and Orthopedic Surgeons

IntroductionGeneral surgeons (GS), orthopedic surgeons (OS), and vascular surgeons (VS) can perform below-knee amputation (BKA) operations. We compared the outcomes of BKA patients among the three specialties. MethodsAdult patients who underwent a BKA were identified from the 2016–2018 National Surgical Quality Improvement Project database. Statistical data for orthopedic and vascular BKA cases were then compared with GS cases using logistic regression analysis. Outcomes included mortality, length of hospital stay, and complications. ResultsThere were 9619 BKA cases. VS had the highest volume of BKA with 58.9% of the cases, compared to GS at 22.9% and OS at 18.1%. 4.4% of general surgery patients had severe frailty compared to OS (3.3%) and VS (3.4%, P < 0.001). VS has the lowest rates of emergency cases (11.9% versus 16.1 for GS versus 15.8% versus OS) and the most favorable wound classification (38.3%, versus 48.7% for GS and VS). Peripheral vascular disease was notably highest in VS (34.0% versus. 20.6% for GS and 9.9% for OS, P < 0.001). Compared to GS, VS was more likely to have a prolonged length of stay (odds ratio) (OR)(1.409), 95% CI 1.265-1.570) while OS was less likely (OR 0.650, 95% CI 0.561-0.754). OS had a lower risk of complications (OR 0.781, 95% CI 0.674-0.904). Mortality was not significantly different among the three specialties. ConclusionsThe National Surgical Quality Improvement Project retrospective analysis of BKA cases suggested that mortality was not statistically different when performed by VS, GS, and OS. There were fewer overall complications when OS performed a BKA, but this is more likely a result of operating upon a generally healthier patient population with lower incidence of preoperative comorbid conditions.

Transition of the epidemiological profile of maternal and congenital syphilis in the State of Goiás (2009-2018): a retrospective analysis

Introduction: Syphilis is a bacterial infection transmitted sexually and transplacental. In Brazil, in the last decade, there has been an increase in notifications of maternal (MS) and congenital (SC) syphilis. Aim: To analyze the epidemiological profile of reported cases of GS and CS in the historical series, from 2009 to 2018, in the state of Goiás. Outlining: Epidemiological, cross-sectional, and analytical retrospective study that describes and analyses the data on MS and CS available in the Information System for Notifiable Diseases (SINAN). Contingency tables, descriptive and inferential statistics were presented, with the application of the G Test and significance level ≤0.05. Results: The results highlighted epidemiological changes in the sociodemographic profile and in the data of the care of pregnant women with syphilis. Implications: The evidenced epidemiological transition shows that there was an improvement in prenatal care in the state of Goiás, requiring health policy measures for specific risk groups. It is fundamental to plan and implement strategic actions with the redefinition of priorities in relation to the epidemiologically affected groups.

A case of Gitelman syndrome with membranous nephropathy

BackgroundGitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN).Case presentationWe described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted.ConclusionsRenal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.

Gitelman syndrome: A first published clinical association with chronic pancreatitis, a case report and review of literature.

Introduction and importanceGitelman syndrome (GS) is an autosomal recessive, salt-losing tubulopathy, also referred to as familial hypokalemia-hypomagnesemia, caused by mutation of genes encoding the sodium chloride cotransporter (NCCT) and magnesium transporters in the thiazide sensitive segments of the distal convoluted tubule (DCT) of the nephron. Patients may present with a spectrum of clinical presentations and associations.Case presentationHere, we report a case of a 39-year-old female with Gitelman syndrome and chronic pancreatitis in the absence of well-known causes of CP. Her clinical and radiographic profile constituted an indication for surgical intervention, namely pancreatic head and body coring and pancreaticojejunostomy (Frey's procedure) (FP). On follow up 3 month later, the patient is pain-free and is satisfied. To the best of our knowledge and based on literature review, this is the first reported case of GS with CP.ConclusionThe purpose of this paper is to describe a case of CP in association with established GS as a first published clinical association, raising a possibility of another possible clinical manifestation of GS. Further observational studies are encouraged to support this association.

Facial Neuritis as a Manifestation of Gradenigo's Syndrome

AbstractGradenigo's syndrome (GS) is a rare, acquired syndrome caused by middle ear infections or mastoiditis. It is identified by the triad of otorrhea due to otitis media (OM), retro-orbital pain in the region innervated by the first and second divisions of the trigeminal nerve, and diplopia as a result of cranial nerve (CN) VI palsy. As a result of extension of the inflammation, the facial nerve (VII) may also be affected. GS has a poor prognosis unless promptly diagnosed and treated. Herein, we report the clinical and radiological findings observed in two children diagnosed with chronic suppurative OM, mastoiditis, and facial neuritis. Both were medically managed as cases of GS with high-dose intravenous antibiotic and full recovery was achieved a few weeks after discharge. There was no need for any surgical intervention. This case report illustrates the importance of early recognition, diagnosis, and treatment of this treatable syndrome using antibiotics to prevent subsequent fatal complications and further need for surgical intervention.

Basaloid follicular hamartomas in pediatric Basal Cell Nevus Syndrome: A diagnostic challenge.

Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant inherited disease caused by PTCH1 (9q22.3‐q31) germline mutations. Skin manifestations are mainly characterized by hyperkeratosis of the palms and soles, palmoplantar pits and a strong predisposition to develop multiple basal cell carcinomas (BCCs). Recently, it has been hypothesized that basaloid follicular hamartomas (BFH) could be included in BCNS skin features. We present three pediatric cases of GS with BCCs and BFHs. Clinical, dermoscopic and immunohistochemical tools are reported.

Clinicopathologic features of Good’s syndrome: Two cases and literature review

BackgroundGood’s syndrome (GS) is an immunodeficiency disease, causing thymoma, low or absent B-cells, hypogammaglobulinemia, and defects in cell-mediated immunity. The most common clinical presentation is recurrent infection, followed by refractory diarrhea, due to the immunodeficiency. However, there are only few reports on intestinal endoscopy and pathology.Case summaryWe report here two typical GS cases with diarrhea as the prominent manifestation. Both cases presented with thymoma combined with immunodeficiency, characterized by hypogammaglobulinemia, low or absent B lymphocytes, and decreased T-cells with inverted CD4+/CD8+ T-cell ratio, while two GS patients were evaluated by endoscopy revealed mucosal edema and fine-granular or nodular appearance changes in the small intestine. Histological examination showed chronic inflammation and villous atrophy. A very interesting finding is that the inflammatory cell infiltration in the two GS cases was different. In one case, predominantly CD138+ plasma cells with only scattered CD3+ T-cells infiltration were revealed, while in another, it showed predominantly T-cells infiltration without plasma cells in the lamina propria. Although GS cases shared various clinical characteristics with common variable immunodeficiency (CVID) cases, they still differed from CVID cases in terms of its late onset, lack of familial clusters, low or absent peripheral blood B lymphocytes, absence of lymphoid hyperplasia, and plasma cells infiltration in the lamina propria in some patients. Although both patients had been diagnosed previously with recurrent diarrhea, respiratory infection, and thymoma, the association between these conditions and the possibility of GS was not recognized. The patients had remained misdiagnosed for 2 and 4 years, respectively, even after receiving the diagnosis of thymoma. The rarity of GS was likely the primary cause for the lack of disease recognition. Reporting of these cases will help to alert clinicians and raise awareness of this disease.ConclusionGS should be considered among the differential diagnoses for patients with unexplained recurrent diarrhea and opportunistic infection. Although it was regarded as a subset of CVID with thymoma, GS had a different clinical-pathological feature from CVID.

Kidney stones and moderate proteinuria as the rare manifestations of Gitelman syndrome

BackgroundGitelman syndrome (GS) is an autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we describe, for the first time, a case of GS without Gitelman-like features and with concomitant kidney stones, cysts and diabetic nephropathy (DN).Case presentationWe described a male patient had a 19-year history of recurrent fatigue. From childhood, he had polydipsia and polyuria, paroxysmal tetany and palpitation. Serum biochemistry revealed chronic hypokalemia, metabolic alkalosis, normomagnesemia, mildly elevated Cr. Concomitant 24 h urine collection showed inappropriate renal potassium wasting, borderline hypercalciuria, moderate proteinuria consisting of major glomerular. Ultrasound of urinary tract showed bilateral and multiple kidney stones and cysts. Whole exome sequencing (WES) identified compound heterozygous mutations of SLC12A3. The unusual association of SLTs and glomerular proteinuria prompted us to perform a renal biopsy. Renal pathology showed renal involvement consistent with GS and early stage of diabetic nephropathy (DN). After treatment with KCl, magnesium oxide, perindopril and acarbose, the patient had been cured. The fatigue didn’t relapse.ConclusionGS had high variability of phenotype, GS may have no Gitelman-like features, kidney stones are not the exclusion criteria of GS. Renal biopsy should be warranted for GS patients with moderate to massive glomerular proteinuria.

Targeted Sequencing of 7 Genes Can Help Reduce Pathologic Misclassification of MDS

Targeted Sequencing of 7 Genes Can Help Reduce Pathologic Misclassification of MDS

Disseminated Mycobacterium abscessus subsp. massiliense infection in a Good\u2019s syndrome patient negative for human immunodeficiency virus and anti-interferon-\u03b3 autoantibody: a case report

BackgroundGood’s syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies.Case presentationA 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies.ConclusionsSince myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

SUN-LB133 Analysis of Clinical Characteristics and Gene Mutation in Four Cases of Gitelman Syndrome

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by renal salt wasting with secondary hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria. GS was found to be caused by mutations in SLC12A3 encoding the thiazide-sensitive sodium chloride cotransporter (NCCT) on the apical membrane of distal convoluted tubule. The prevalence worldwide is estimated at approximately 1:40,000, making it one of the most frequent inherited renal tubular disorders. To date, over 400 mutations scattered throughout SLC12A3 have been identified in GS patients. The majority of patients are compound heterozygous for SLC12A3 mutations, but a significant number of GS patients are found to carry only a single SLC12A3 mutation. The type of the SLC12A3 mutation may be a determinant factor in the severity of GS. The purpose of this study is to analyze clinical characteristics and gene mutation in four cases of GS. Methods: Four patients with closely resembling Gitelman syndrome was selected. Results: Six SLCl2A3 gene mutations were found in these four patients. There were one SLCl2A3 homozygous mutation in case 1 and case 3, and two SLCl2A3 heterozygous mutations in case 2 and case 4, respectively. This six gene mutations include missense mutations, frameshift mutations, and nonsense mutations. Four patients were diagnosed with Gitelman syndrome. Case 4 is the most severe with severe hypokalemia, accompanied by ventricular arrhythmias, which may be related to the presence of two SLC12A3 gene mutations in the patient. Conclusions: Four patients in this study were diagnosed with Gitelman syndrome based on their clinical characteristics and genetic testing results. For patients with hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria need to exclude Gitelman syndrome.Key words: Gitelmen Syndrome, Mutations, SlC12A3 gene

The Potential Impact of Plastic Surgery Expertise on Body Contouring Procedure Outcomes.

With the increasing demand for body contouring procedures in the United States over the past 2 decades, more surgeons with diverse specialty training are performing these procedures. However, little is known regarding the comparative outcomes of these patients. The purpose of this study was to compare outcomes of body contouring procedures based on the specialty training of the surgeon. Data from the American College of Surgeons National Surgical Quality Improvement Program (2005-2015) were reviewed for all body contouring procedures. Patients were stratified by surgeon training (plastic surgery [PS] vs general surgery [GS]). Descriptive statistics and regression analyses were used to evaluate differences in outcomes. A total of 11,658 patients were included; 9502 PS cases and 2156 GS cases. Most were women (90.4%), aged 40 to 59 (52.7%) and white (79.5%). Compared with PS patients, GS patients were more likely to be obese (61.4% vs 40.6%), smokers (13.6% vs 9.8%), and with ASA classification ≥3 (35.3% vs 18.6%) (all P < 0.001). Abdominal contouring procedures were the most common (76%) cases. Multivariate regression revealed that compared with PS cases, those performed by GS practitioners were associated with increased wound and infectious complications (adjusted odds ratio [aOR], 1.81; 95% confidence interval [CI], 1.44-2.27), reoperation (aOR, 1.85; 95% CI, 1.31-2.62), and predicted mean length of stay (1.12 days; 95% CI, 0.64-1.60 days). The variable outcomes in body contouring procedures performed by PS compared with GS practitioners may imply procedural-algorithmic differences between the subspecialties, leading to the noted outcome differential.

Goldenhar syndrome: rare case reported from secondary health care facility in Himachal Pradesh

Dr. Maurice Goldenhar, a renowned Swiss ophthalmologist classified the clinical features and named the malformation complex as Goldenhar Syndrome and described it as a congenital defect characterized by constellation of malformations classically involving the face, eyes and ears. Principal deformities of the Goldenhar syndrome are often combined with various malformations, like Cleft lip and/or palate, tongue cleft, unilateral tongue hypoplasia, and parotid gland aplasia, Rib anomalies, Congenital heart disease (ventricular septal defects). A 12-year-old female patient diagnosed with Goldenhar syndrome at secondary care Regional Hospital Bilaspur, Himachal Pradesh. She was diagnosed with a case of Goldenhar syndrome on clinic-radiological investigations. The patient reported to ophthalmology OPD of the hospital with the chief complaint of soft tissue structure in left eye with decreased vision. On examination limbal dermoid was observed. Patient was having pre-auricular tissue tag on both sides, hemifacial micrognathia and microstomia. Correlating the history and physical findings a provisional diagnosis of Goldenhar Syndrome was made with differential diagnosis of Franschetti syndrome or Treacher – Collins syndrome, Nager syndrome or acro-facial dysostosis and Townes-Brocks syndrome. Based on the clinical and radiographic findings a diagnosis of Goldenhar syndrome was made. Severe cases of GS can affect the routine and social life of the patient. Early detection can help avoid complications at a later stage of life. Such patients will have an increased risk for psychosocial difficulties. The study of this condition is still controversial because the symptoms and the physical features may vary greatly in range and severity from case to case.

The comparative study of in transition zone prostate cancer: diagnostic performance of new intravoxel incoherent motion and diffusion kurtosis imaging models

Objective To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters in diagnosing prostate cancer(PCa) in transition zone (TZ) and stratifying pathologic Gleason grade of prostate cancer. Methods A total of 55 patients who were undergoing preoperative muti-parameters MRI of T2WI, DWI, IVIM and DKI model for the exploration of prostate cancer (January 2015 to June 2017) with pathologically confirmed by MRI-transrectal ultrasound (TRUS) targeted fusion biopsy were retrospectively included. Parameters were postprocessed by IVIM models including quantitation of perfusion fraction (f), diffusivity (D) and pseudo-diffusivity (D*) and DKI models including the mean diffusivity (MD), mean kurtosis (MK) and fractional anisotropy (FA) by outlining the 3D VOI. Independent sample t-test was used to compare the differences in lesion parameters between prostate cancer and BPH, low-risk (BPH+Gleason score 6 points) and medium-high-risk lesions (Gleason score ≥7 points). Correlation between ADC values, IVIM and DKI parameters and Gleason scores were assessed with Spearman analysis. Receiver operating characteristic curve analysis was used to evaluate the efficacy of various parameters in the differential diagnosis of prostate cancer and BPH with low-risk or high-risk. Results 27 (36 focus) cases of PCa and 28 (40 focus) cases of benign prostatic hyperplasia (BPH) in PZ were included, meanwhile, the cases of GS ≥7 and and BPH+(GS=6) were 33,43,respectively. There were significant differences in ADC, D, MD, MK, and FA between patients in PCa-BHP group and high-low risk group in TZ (P 0.05). ADC and MD showed relatively higher negativity correlations (r were -0.585 and -0.489, P 0.05). Of model DKI in diagnose of PCa and BPH, the highest classification accuracy was MD(AUC 0.796). The AUC derived from multiple model parameters in different combination of ADC+D value, ADC+MD value, and ADC+MD+D value were 0.892, 0.884, and 0.897, respectively. ADC and D of IVIM model showed a significance difference between GS ≥7 and BPH+(GS=6) with a higher AUC of 0.826 and 0.743. The AUC was 0.851 of the combination of mean ADC and D, 0.846 of combination of mean ADC and MD, the AUC (0.856) of the combination of ADC, D and MD significant higher than any two combined parameters (P>0.05). Conclusions IVIM and DKI models may help to discriminate prostate cancer from BPH, and predict mid-higher GS PCa in TZ. But there is no significant advantage compared with ADC values. It is feasible to stratify the pathological grade of prostate cancer in TZ by mean ADC and MD. Key words: Prostate neoplasms; Benign prostatic hyperplasia; Intravoxel incoherent motion; Diffusion kurtosis imaging

Digenetic inheritance of SLC12A3 and CLCNKB genes in a Chinese girl with Gitelman syndrome

BackgroundGitelman syndrome (GS) is an autosomal recessive disorder and mild variant of classic Bartter syndrome. The latter is caused by defects in the genes CLCNKB and/or CLCNKA (chloride voltage-gated channel Ka and Kb). Patients with GS usually have loss-of-function mutations in SLC12A3. No patient has been reported with compound heterozygous mutations in these genes. We report a girl with GS with a paternally inherited heterozygous mutation in SLC12A3, and maternally inherited heterozygous variants in both CLCNKB and CLCNKA.Case presentationIn this report, we reported a female patient (8 y and 10 mo) who had growth retardation (111.8 cm, − 1.62 standard deviation height for age) and normal blood pressure, with persistent hypokalemia, hypomagnesemia, hypocalciuria, hypochloremic alkalosis, and elevated levels of plasma renin and aldosterone. Her younger brother, father, and paternal grandmother all had histories of mild low levels of plasma potassium (3.0–3.5 mmol/L), which were rectified by potassium-rich foods. The genomic DNA of the patient, younger brother, parents, and grandparents were screened for gene variations and pedigree analysis using trio whole exome sequencing (WES). The candidate variants were validated by Sanger sequencing. Protein-protein interaction analysis utilized the following databases: Biogrid, MINT, HPRD, STRING, IntAct, iRefIndex, and ppiTrim. The trio WES screening showed that the patient has paternally inherited SLC12A3 p.N359K, and maternally inherited CLCNKB p.L94I. The paternal grandmother and younger brother are both carriers of SLC12A3 p.N359K. According to the STRING database, SLC12A3 and CLCNKB proteins may interact or coexpress with proteins associated with GS.ConclusionsBased on clinical phenotypes, genetic evidence of the pedigree, and previous reported studies, this case of GS indicates a digenetic inheritance of SLC12A3 and CLCNKB that resulted in renal tubular dysfunction perhaps, due to a genetic double-hit mechanism. The putative pathogenicity of the CLCNKB p.L94I variant requires confirmation.

Mother-to-child transmission and gestational syphilis: Spatial-temporal epidemiology and demographics in a Brazilian region.

Syphilis is a Sexually Transmitted Infection (IST) with significant importance to public health, due to its impact during pregnancy (Gestational Syphilis—GS); especially because syphilis can affect fetus and neonates’ development (mother-to-child transmission—MTCT of syphilis), by increasing susceptibility to abortion, premature birth, skeletal malformations, meningitis and pneumonia. Measures to control and eliminate MTCT of syphilis have failed on the last few years in Brazil and this research aimed to identify the seasonality of notified cases of syphilis in a region of São Paulo state. The studied region, Pontal do Paranapanema, comprises 32 cities located in the West of São Paulo state, in Brazil. Data collected from the National System of Aggravations and Notification (SINAN) website was used to calculate the incidence rate of GS and MTCT. The incidence rate of GS was acquired dividing number of cases by number of women in each municipality and MTCT using number of live births in each year (from 2007 to 2013) in each municipality. This result was then, standardized multiplying incidence rate by 10,000 and expressed as incidence/10,000 women or live births, for GS and MTCT, respectively. To identify possible endemic/epidemic periods, a control diagram was performed using the standard deviation (SD) of incidence rate. Thematic maps representing the spatial distribution of incidence rates were constructed using a Geographic Information System software (GIS, based on cartographic vector available on the Brazilian Institute of Geography and Statistics (IBGE) website. Eighty cases of GS and 61 cases of MTCT were notified in the studied region. An increase of GS notification was detected in the Pontal do Paranapanema in 2011 followed by an increase in number of MTCT cases in the subsequent year, suggesting inefficacy in the treatment during gestational period. Most of those cases were reported on February and November which suggested seasonality for this IST in the region. The control diagram, based on the inputs collected from SINAN, showed no endemic period; however, the most susceptible month to happen an endemic event of GS and MTCT was February. Our study provided a new methodology to understand the syphilis dynamics as a potential tool to improve the success of future measures to control and possibly eliminate MTCT of syphilis.