A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family

●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.

Two big orifices in the second duodenal portion:A case of an atypical double papilla

With the advent of endoscopic retrograde cholangiopancreatography(ERCP)in the early 1970s,anatomic anomalies of the Vaterian system were described endoscopically[1].Although the occurrence is rare,the common bile duct(CBD)and the pancreatic duct may fail to coalesce during embryologic development.This leads to double major papilla because both ducts open into the duodenum separately[1].In this way the cranial duct communicates with the CBD,while the caudal orifice communicates with the pancreatic duct[2].

Neuroimaging in atypical normal tension glaucoma:debating routine implementation in the absence of classic neurological findings

●AIM:To assess the necessity of neuroimaging in patients with neurological or atypical findings of normal tension glaucoma(NTG)who do not exhibit typical glaucoma manifestations.●METHODS:A retrospective analysis was conducted on 90 atypical NTG patients who underwent cranial magnetic resonance imaging(MRI)due to atypical symptoms.The demographic characteristics,clinical parameters,and radiological findings were recorded.●RESULTS:Among the patients,66.7%had abnormal radiology results,with the most common findings being gliosis(34.4%),sequelae of cerebrovascular events and vascular malformations(14.4%),and benign intracranial mass lesions(11%).Non-glaucomatous visual field defects were more frequently observed in patients with abnormal neuroimaging results.However,there were no significant differences in intraocular pressure,optic disc parameters,retinal nerve fiber layer thickness,and visual field indices between patients with normal and abnormal radiological results.The mean age of the patients was 58.74y.Interestingly,there was a significant age difference,with the abnormal radiology group having a higher median age(P=0.021).●CONCLUSION:The study highlights the importance of cranial imaging in older NTG patients to detect underlying pathologies and prevent misdiagnosis.It suggests that neuroimaging may be warranted in NTG patients with atypical visual field defects incompatible with glaucoma.However,routine neuroimaging in all NTG patients without classic neurological signs may not be necessary.

Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

Increased Risk of Neonatal Pneumonia in Pregnant Women with Atypical Pre-Labor Rupture of Membrane Assessed at Pregnancy Week 39

Purpose: Neonatal pneumonia is a major newborn disease with a high morbidity rate. We aimed to evaluate whether atypical prelabor rupture of membranes (PROM) is a high-risk factor for causing neonatal pneumonia in a prospective real-world study. Patients and Methods: A total of 250 pregnant women at pregnancy week 39 were non-selectively recruited. All were examined by PROM and neonatal pneumonia related clinical, bedside and lab tests, including body temperature, blood pressure, increased vagina discharge, posterior vault pooling, abdominal tenderness, WBC count, nitrazine test, amniotic fluid index, Leakection (a sICAM-1 based lateral flow immunoassay) and vagina streptococcus examinations. Increased vagina discharge with a Leakection positivity was adopted as a working criterium for identifying atypical PROM. Neonatal pneumonia was diagnosed based on the clinical presentation and lab tests. Results: Twenty cases of neonatal pneumonia (8.0%) were diagnosed after the deliveries of the 250 pregnant women. In these neonatal pneumonia cases, 12 (16.7%) occurred in 72 deliveries with atypical PROM, 2 (16.7%) in 12 deliveries with typical PROM, and 6 (3.6%) in 166 deliveries with non-PROM. Conclusion: In this real-world study, we find that a systematic screening at pregnancy week 39 was very meaningful in revealing atypical PROM. Moreover, atypical PROM is a major risk factor for neonatal pneumonia. Therefore, an early diagnosis and intervention on atypical PROM could potentially reduce the occurrence of neonatal pneumonia.

A multiplex real-time PCR assay for simultaneous detection of classical swine fever virus,African swine fever virus,and atypical porcine pestivirus

With the implementation of the C-strain vaccine,classical swine fever(CSF) has been under control in China,which is currently in a chronic atypical epidemic situation.African swine fever(ASF) emerged in China in 2018 and spread quickly across the country.It is presently occurring sporadically due to the lack of commercial vaccines and farmers’ increased awareness of biosafety.Atypical porcine pestivirus(APPV) was first detected in Guangdong Province,China,in 2016,which mainly harms piglets and has a local epidemic situation in southern China.These three diseases have similar clinical symptoms in pig herds,which cause considerable losses to the pig industry.They are difficult to be distinguished only by clinical diagnosis.Therefore,developing an early and accurate simultaneous detection and differential diagnosis of the diseases induced by these viruses is essential.In this study,three pairs of specific primers and Taq-man probes were designed from highly conserved genomic regions of CSFV(5’ UTR),African swine fever virus(ASFV)(B646L),and APPV(5’ UTR),followed by the optimization of reaction conditions to establish a multiplex real-time PCR detection assay.The results showed that the method did not cross-react with other swine pathogens(porcine circovirus type 2(PCV2),porcine reproductive and respiratory syndrome virus(PRRSV),foot-and-mouth disease virus(FMDV),pseudorabies virus(PRV),porcine parvovirus(PPV),and bovine viral diarrhea virus BVDV).The sensitivity results showed that CSFV,ASFV,and APPV could be detected as low as 1 copy μL–1;the repeatability results showed that the intra-assay and interassay coefficient of variation of ASFV,CSFV,and APPV was less than 1%.Twenty-two virus samples were detected by the multiplex real-time PCR,compared with national standard diagnostic and patented method assay for CSF(GB/T 27540–2011),ASF(GB/T 18648–2020),and APPV(CN108611442A),respectively.The sensitivity of this triple real-time PCR for CSFV,ASFV,and APPV was almost the same,and the compliance results were the same(100%).A total of 451 clinical samples were detected,and the results showed that the positive rates of CSFV,ASFV,and APPV were 0.22% (1/451),1.3%(6/451),and 0%(0/451),respectively.This assay provides a valuale tool for rapid detection and accurate diagnosis of CSFV,ASFV,and APPV.

Iridociliary Body Metastasis of Atypical Carcinoid: Case Management with Intravitreal Anti-Vascular Endothelial Growth Factor Injections

We report a rare case involving a 52-year-old female diagnosed with an atypical bronchial carcinoid tumor with metastases to the mediastinum, hilar lymph nodes, breast, and pancreas. In additional, the patient had metastases to the iris and ciliary body, resulting in progressive vision loss in her left eye. Treatment was successful by intravitreal injections of anti-vascular endothelial growth factor.

From precise diagnosis to effective treatment:a case report of atypical Cogan's syndrome

Dear Editor,We present the reported case of a 37-year-old male atypical Cogan’s syndrome(CS)patient who was precisely diagnosed and clinically cured under our systematic therapeutic regime.CS is a rare autoimmune disorder involving the eye,characterised by interstitial keratitis(IK)and the auditory-vestibulo system with vestibular dysfunction.

Surgical strategy of the treatment of atypical femoral fractures

The atypical femoral fracture(AFF)has been attracting significant attention because of its increasing incidence;additionally,its treatment is challenging from biological and mechanical aspects.Although surgery is often required to manage complete AFFs,clear guidelines for the surgical treatment of AFFs are currently sparse.We reviewed and described the surgical treatment of AFFs and the surveillance of the contralateral femur.For complete AFFs,cephalomedullary intramedullary nailing spanning the entire length of the femur can be used.Various surgical techniques to overcome the femoral bowing common in AFFs include a lateral entry point,external rotation of the nail,and the use of a nail with a small radius of curvature,or a contralateral nail.In the case of a narrow medullary canal,severe femoral bowing,or pre-existing implants,plate fixation may be considered as an alternative.For incomplete AFFs,prophylactic fixation depends on several risk factors,such as a subtrochanteric location,presence of a radiolucent line,functional pain,and condition of the contralateral femur;the same surgical principles as those in complete AFFs can be applied.Finally,once AFF is diagnosed,clinicians should recognize the increased risk of contralateral AFFs,and close surveillance of the contralateral femur is recommended.

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia:A case report and review of literature

BACKGROUND Zollinger–Ellison syndrome(ZES)results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors,commonly referred to as gastrinomas.The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum.Here,we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma.CASE SUMMARY A 72-year-old woman presented with the typical clinical manifestations of ZES,including upper abdominal pain,significant watery diarrhea,and acidic liquid vomitus.Surprisingly,however,she did not have an increased level of serum gastrin.In addition,there was no evidence of gastrinoma or any other ulcerogenic tumor.Esophagogastroduodenoscopy was conducted to examine the upper digestive tract.Revised diagnoses were considered,and an individualized treatment plan was developed.The patient responded to antacid medication while experiencing intermittent,recurring bouts of ZES.18F-AlF-NOTAoctreotide positron emission tomography(18F-OC PET)/computed tomography(CT)helped locate the tumor.Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site.CONCLUSION This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia.18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome:A case report and review of literature

BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.

Characterization of Atypical Individuals of Lannea in Burkina Faso

Background and Objectives: The species to the Lannea genus are trees, shrubs with compound leaves. Thus, individuals called atypical Lannea with single leaves and of socio-economic interests have been identified in the central plateau region (Burkina Faso). This study aimed to contribute to the identification of atypical species. Material and Methods: The Polymerase Chain Reaction (PCR) method using specific primers was performed and consisted of extracting DNA from young leaves of Lannea individuals, amplifying and then sequencing portions of discriminating DNA (matK, rbcL and rps16). Results: It was shown that individuals belong to the Lannea genus, but are subdivided into three subgroups: a first subgroup containing Lannea microcarpa and two subgroups with no previously identified Lannea species. Conclusion: These atypical individuals are ecotypes or mutants of Lannea microcarpa.

Atypical eclampsia at primary health care in a remote area:A case report

BACKGROUND Eclampsia is a generalized tonic-clonic seizure induced by pregnancy.It contributes to a high rate of maternal and neonatal morbidity and mortality worldwide.Eclampsia is characterised by classic signs such as elevated blood pressure,proteinuria,and seizures.However,it may occur in the absence of hypertension and/or proteinuria.The uncommon appearance of eclampsia makes it difficult to immediately assess and treat it.In addition,the occurrence of this case in a remote area makes it more challenging to handle.The objective of this case report is to increase awareness of uncommon manifestations of eclampsia,particularly in limited-resource settings.CASE SUMMARY A young primigravida experienced a generalised seizure without hypertension and/or proteinuria.Sudden hearing loss,blurred vision,and vomiting were complained about before the seizure attack.The patient was diagnosed with eclampsia.A loading dose of magnesium sulphate was administered immediately.The patient was referred from community healthcare to a hospital and discharged without any complications.CONCLUSION Atypical eclampsia may be a diagnostic challenge.However,other symptoms may be beneficial,such as awareness of eclampsia signs.

Atypical Symptoms of Early Onset Bipolar Disorder

Juvenile bipolar disorder can be a challenging diagnosis, given its atypical presentation and tendency to have other comorbid psychiatric disorders. In this case study, we describe a case of a young patient with some atypical symptoms of early-onset bipolar disorder.

An Incidental Finding and Unusual Presentation of Atypical Coccidioidomycosis in a 72-Year-Old Man: A Case Report

This case report presents an unusual and challenging diagnostic scenario involving a 72-year-old man who recently returned from a trip to Maui, Hawaii. While in Maui, the patient presented with a fever and fatigue that resolved spontaneously. However, he had an observable rash on his head and was given a steroid injection to resolve the rash. Later on his trip, the patient experienced a dry, nonproductive cough which resolved with a five-day course of prednisone. While visiting Michigan, the patient began to experience neck pain and visited Troy Beaumont Hospital for further treatment. Meningitis tests were negative. Vancomycin was given due to the detection of gram positive coccidioidomycosis in the culture, but this was later proven to be a contaminant. Coccidiomycosis does not initially have specific symptoms. Despite negative coccidioidomycosis antigen tests, the patient exhibited features more consistent with blastomycosis and cryptococcus, highlighting the complexities of diagnosing fungal infections with atypical presentations. The case emphasizes the importance of considering alternative fungal pathogens native to endemic regions and pursuing comprehensive diagnostic measures to establish an accurate diagnosis. Lastly, the discussion about recommendations for antifungal therapy and preventative measures for individuals at risk of respiratory fungal infections is critically important for the advancement of early detection of fungal infections.

Atypical Hemolytic Uremic Syndrome in a Patient with Acute Promyelocytic Leukemia: A Case Report

Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.

Current concepts in the management of bisphosphonate associated atypical femoral fractures

Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone.Whilst aiming to reduce the risk of fragility fractures,bisphosphonates have been associated with atypical insufficiency fractures,specifically in the femur.Atypical femoral fractures occur distal to the lesser trochanter,until the supracondylar flare.There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures,indicating that there is a distinct difference in the respective underlying pathophysiology.At the point of presentation of an atypical femoral fracture,bisphosphonate should be discontinued.This is due to the proposed inhibition of osteoclasts and apoptosis,resulting in impaired callus healing.Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity.Nutritional deficiencies should be investigated and appro-priately corrected,most notably dietary calcium and vitamin D.Currently there is no established treatment guidelines for either complete or incomplete fractures.There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes.Currently,the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation.Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex,with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share,and a reduced bending moment across the fracture site.The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates.However,it is important to appreciate that the anatomical location and patient factors may not always allow for this.Although causation between bisphosphonates and atypical fractures is yet to be demonstrated,there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates.As we encounter a growing comorbid elderly population,the prevalence of this fracture-type will likely increase.Therefore,it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.

MRI and Transvaginal Ultrasound Findings of Atypical Polypoid Adenomyoma: A Case Report

Atypical polypoid adenomyoma(APA)is an uncommon type of polypoid characterized by fibroid stroma and endometrial glands.It occurs mostly in premenopausal women and rarely in postmenopausal women with irregular vaginal bleeding.In our current case,a 76-year-old woman presented with irregular vaginal bleeding.The final pathological diagnosis of the mass was APA.APA is not easy to diagnose before surgery.On the one hand,there was no obvious particularity in imaging features and clinical features,especially for uncomfortably identifying endometrial cancer.On the other hand,APA has a pedicle,attaching to any part of the uterine cavity,which can cause pseudocoel between the mass with the uterine cavity wall.So,when it comes to getting the pathological tissue in the absence of hysteroscopy,it is easy to access to the pseudocoel and obtain endometrial tissue rather than the pathological tissue of the mass.Therefore,preoperative imaging examination is of great significance diagnosis way of thinking to clinicians for APA.In the meantime,pathological tissue of APA can be obtained by hysteroscopy in visual conditions.

Chinese family with atypical granular corneal dystrophy type I caused by the typical R555W mutation in TGFBI

·AIM: To investigate the clinical features and genetic defects in four generations of a Chinese family affected with atypical granular corneal dystrophy type I (GCD type I). · METHODS: Family history and clinical data were recorded. Genomic DNA samples were obtained from peripheral blood leukocytes of all participated. Exons of the transforming growth factor-β-induced (TGFBI) gene were directly sequenced after being amplified by polymerase chain reaction (PCR), and multi-point linkage analysis using microsatellite makers flanking the gene was applied to identify the disease-causing mutation. · RESULTS: Clinical features were quite variable in patients, some patients only had opacities in the epithelium, and others revealed multiple bilateral circular, discrete, crumb -like opacities mainly in the epithelium, with several in different depths of corneal stroma, and the performance was different bilaterally, even in the same patient. Directly nucleotide sequencing revealed a heterozygous p.R555W mutation in the coding sequence of the TGFBI gene in all affected individuals of the family, but was not found in all unaffected. The maximum logarithm of odds (LOD) score obtained by multi -point analysis was detected at marker locus D5S393 (LOD = 2.740; α=1.000). ·CONCLUSION: Our case presented with clinical futures and the pathogenic mutations in TGFBI gene, the phenotype of the pedigree was quite different from typical GCD type I, so we suggested that this phenotype was a variant of GCD type I. These findings expand the knowledge about GCD type I, and demonstrate that molecular genetic analysis is important to make an accurate diagnosis of patients with variable corneal dystrophies in clinic.

Safety and related factors of treatment with long-term atypical antipsychotic in Chinese patients with schizophrenia:observational study

Background Atypical antipsychotics as first-line drugs have been used in patients with schizophrenia in China and abroad.However,its safety still needs to be evaluated in a large population,especially in Chinese patients.Objective The main objective of this study is to evaluate the safety and related factors of long-term atypical antipsychotic use in patients with schizophrenia in China.The secondary objective includes the long-term efficacy of atypical antipsychotics in these patients,as well as pharmacoeconomic evaluation,population pharmacokinetic studies and pharmacogenomics studies.Methods This study has an observational design.The atypical antipsychotics include quetiapine,olanzapine,risperidone,aripiprazole,ziprasidone,paliperidone,amisulpride,perospirone and clozapine.Visits occur at 0,4,8,13,26,52,78,104,130 and 156 weeks.The efficacy evaluations include symptoms,social function,recurrence rate and hospitalisation.The safety measures include physical examination,vital signs,abdominal circumference,laboratory tests(such as blood cell analysis,blood biochemical tests and serum prolactin/thyroxine levels),12-lead ECG,extrapyramidal syndrome assessment,sexual function evaluation,medication and other adverse events.The secondary measures include the Positive and Negative Syndrome Scale,Clinical Global Impression-Severity of Illness Scale,Calgary Depression Scale for Schizophrenia,Personal and Social Performance Scale,relapse rate,drug consolidation,medical-related expenses,income,drug plasma concentration and genetic information.Results This is a large sample,non-interventional and long-term prospective clinical study designed to truly reflect the specific details of clinical practice,fully respect patients’needs,and understand patients’treatment intentions and actual treatment details.Conclusions This research method details the aims,methods,study design,strengths and limitations of the study.