Rare Feature Research Articles

DFML: Dynamic Federated Meta-Learning for Rare Disease Prediction.

Millions of patients suffer from rare diseases around the world. However, the samples of rare diseases are much smaller than those of common diseases. Hospitals are usually reluctant to share patient information for data fusion due to the sensitivity of medical data. These challenges make it difficult for traditional AI models to extract rare disease features for disease prediction. In this paper, we propose a Dynamic Federated Meta-Learning (DFML) approach to improve rare disease prediction. We design an Inaccuracy-Focused Meta-Learning (IFML) approach that dynamically adjusts the attention to different tasks according to the accuracy of base learners. Additionally, a dynamic weight-based fusion strategy is proposed to further improve federated learning, which dynamically selects clients based on the accuracy of each local model. Experiments on two public datasets show that our approach outperforms the original federated meta-learning algorithm in accuracy and speed with as few as five shots. The average prediction accuracy of the proposed model is improved by 13.28% compared with each hospital's local model.

Anti-leucine-rich Glioma-inactivated 1 Encephalitis Manifesting as Frequent Ictal Pouting and Subtle Memory Disturbance.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a treatable form of limbic encephalitis, marked by frequent focal seizures and cognitive decline (particularly memory disturbance); however, it can be difficult to diagnose in patients with subtle cognitive decline. Ictal pouting, a rare seizure feature, has not yet been reported in anti-LGI1 encephalitis. A 73-year-old man with anti-LGI1 encephalitis presented with subacute onset of frequent ictal pouting without apparent cognitive decline. Steroid treatment alone resolved seizures and improved subtle visual memory. Middle-aged and older patients experiencing subacute-onset frequent focal seizures should be thoroughly evaluated for memory disturbances to determine the need for anti-LGI1 antibody measurement.

Confidence score calculation for the carcinogenic potency categorization approach (CPCA) predictions for N-nitrosamines

We present a method for computing confidence in the Carcinogenic Potency Categorization Approach (CPCA) based predictions for N-nitrosamines. Our method relies on capturing local structural variations surrounding the nitrosamine core, which can significantly influence potency and may introduce uncertainty into predictions relying on these features.We use continuous-valued fingerprints to conduct a specialized neighborhood analysis, grouping nitrosamines with similar local features. Using a reference dataset of 7679 potential Nitrosamine Drug Substance Related Impurities (NDSRIs) with pre-computed CPCA-derived Acceptable Intake (AI) limits, we gauge the prediction confidence for a given query N-nitrosamine by evaluating the distances and CPCA derived potency category distribution among neighboring NDSRIs. Our methodology allows for a nuanced assessment of CPCA's discrete four-level outcomes (i.e. 18/26.5, 100, 400, and 1500 ng AI limits). It enables the differentiation of robust predictions from potentially uncertain ones, for instance, cases where low confidence arises from rare structural features in the query nitrosamine, helpful in regulatory decision-making.In our analysis of 30 nitrosamines with animal carcinogenicity data, we often observed lower confidence scores when experimental TD50 values significantly disagreed with CPCA-calculated potency. Moreover, lower confidence scores were associated with greater variability in the predicted α-carbon hydroxylation potential of neighboring compounds. In a list of 265 NDSRIs with established regulatory AI limits, approximately 68% received strong confidence scores for accurate CPCA potency class predictions. However, 8% received poor confidence in potency class predictions, as well as lacked sufficient neighbor support due to uncommon structural features.

Double modals in Australian and New Zealand English

AbstractThis paper reports the first large‐scale corpus study of double modal usage in Australian and New Zealand Englishes, based on a multi‐million‐word corpus of geolocated automatic speech recognition transcripts from YouTube. Double modals are considered rare grammatical features of English, which have long been extremely difficult to observe in natural language due to low frequencies, non‐standardness, and restriction to oral speech registers. In addition, it has generally been assumed that they make up small sets of diachronically related forms, whose geographical distribution is mainly restricted to the Southern US and the North of the UK. Our results challenge these long‐standing assumptions by presenting the first inventory of double modals observed outside of these regions, thanks to computational sociolinguistic methods. Overall, we identify and map 474 double modal tokens distributed in 51 types, an unexpectedly large collection of forms used with varying frequencies across Australia and New Zealand. We consider the relevance of our results for three specific new claims concerning the diversity, complexity, and origins of double modals in English world‐wide.

A Case of Ramsay Hunt Syndrome Showing Central Findings due to Brainstem Involvement

Ramsay Hunt syndrome occurs when the varicella zoster virus reactivates. Classic findings include the triad of facial paralysis, otic pain and herpetic lesions due to the pathogenesis associated with anterograde axonal reactivation of the varicella zoster virus in the geniculate ganglion. In addition to the classic triad, rare features such as a central type of vestibular function test may be observed due to the retrograde spread of the varicella zoster virus from the geniculate ganglion into the brain stem, including involvement of the vestibular nucleus. We present a case of Ramsay Hunt syndrome in a 57-year-old male patients, manifesting not only the typical triad of symptoms but also the unique features associated with brain stem involvement. This presented as direction-changing gaze-evoked nystagmus and a decrease in gain on both sides on video head impulse test. And brain magnetic resonance imaging showed a lesion in the vestibular nucleus of the brain stem.

IgG4-Related Disease with IgG1-Dominant Membranous Nephropathy: A Rare Case Report

ABSTRACT Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder affecting various organs and tissues. Kidney involvement in IgG4-RD commonly manifests as IgG4-related tubulointerstitial nephritis or IgG4-related membranous nephropathy, with the latter occurring less frequently. The identification of the phospholipase A2 receptor (PLA2R) antigen has improved our understanding of primary membranous nephropathy. Here, we present the case of a 60-year-old Chinese man initially diagnosed with IgG4-related pancreatitis, who achieved clinical remission with glucocorticoid therapy followed by low-dose glucocorticoid maintenance therapy. Two years later, the patient developed nephrotic syndrome. A kidney biopsy revealed membranous nephropathy characterized by glomerular subepithelial deposition of IgG1 and positive PLA2R staining. Rituximab (RTX) treatment resulted in complete clinical remission of nephrotic syndrome, and no recurrence was observed during the 24-month follow-up period. IgG4-RD complicated by membranous nephropathy is a rare pathological feature characterized by glomerular subepithelial IgG1 deposition and positive PLA2R antigen staining. In the present case, RTX treatment was effective in achieving clinical remission. These findings contribute to the evolving understanding of the relationship between IgG4-RD and membranous nephropathy.

A case of lung adenocarcinoma with markedly elevated amylase in airway secretions

A 45-year-old male patient was admitted to the hospital because of intermittent cough and expectoration for more than 1 year, worsened by dyspnea for 2 months, and was finally diagnosed with lung adenocarcinoma. The CT scan of the chest revealed lesions of diversity with fibrosis, mass and effusion, but his severe cough limited biopsy of the lesions. The difficult process of diagnosis was aided by the further analysis of the sputum, which showed significantly elevated amylase without any evidence of pancreatic disease. The cough was relieved by intravenous pumping octreotide acetate, and both CT-guided lung biopsy and transbronchial biopsy revealed the lung adenocarcinoma. The diagnostic process of this case provided a helpful diagnostic thinking and demonstrated the rare clinical features of lung adenocarcinoma.

Cone beam computed tomography evaluation of c-shaped canal morphology in mandibular premolar teeth.

The aim of this study was to evaluate the prevalence and the morphology of c-shaped root canal(s) in mandibular premolars using cone beam computed tomography (CBCT) images. CBCT images of 1095 mandibular premolars were examined at coronal, middle, and apical levels of the root canals. The type, the level, and the position (buccal or lingual) of the c-shaped anatomy were recorded. Absolute counts and percentages of different groups and subgroups of C-shape morphologies were calculated. The Chi-square test was used to compare the prevalence of C-shaped morphology between mandibular first and second premolars. The Z-test for proportions in independent groups was used to analyze the differences in mandibular C-shaped premolar proportions between location (left and right side) and tooth (first or second premolars) (p=0.05). C-shaped root canal morphology was present in 44 teeth. The percentage of c-shaped morphologies was 6.9% and 1.6% in mandibular first and second premolars, respectively. Comparison of the first and the second premolars showed that C1 type (p=0.008) and C4b type (p=0.013) configurations are more common in the first premolars at the coronal level. In contrast, the C2 type configuration showed significantly higher prevalence in the second premolars (p=0.009). Additionally, the C4c type configuration was significantly frequent on the right premolars at the coronal level (p=0.038). C-shape canal morphology is a rare but complex anatomic feature in mandibular premolars. Therefore, clinicians should be aware of this complex root canal anatomy for the success of endodontic treatment in mandibular premolar teeth.

Glomerular lipidosis as a feature of renal-limited macrophage activation syndrome in a transplanted kidney: a case report

BackgroundGlomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.Case presentationA 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient’s extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.ConclusionTo our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.

Megasporogenesis, megagametogenesis and embryogenesis of Liparis elliptica (Orchidaceae), with special note to the development of unique unitegmal ovule.

Megasporogenesis, megagametogenesis and embryogenesis of Liparis elliptica (family Orchidaceae, tribe Malaxideae, subtribe Malaxidinae) have been studied. It was shown that the L. elliptica embryo sac is monosporic and develops from the chalazal cell of the megaspore triad according to the modified Polygonum type. The embryo sacs are reduced to four-six nuclei. The suspensor is unicellular, spherical in shape, originating from the basal cell (cb). A unique feature of L. elliptica is the unitegmal ovule, which distinguishes this species from other members of the tribe Malaxideae. The seed coat is formed by an outer layer of the single internal integument. Reduction of the outer integument is a rare feature for epiphytic orchid species with photosynthetic leaves.

Expanded phenotypic spectrum of FOXL2 Variant c.672_701dup revealed by whole-exome sequencing in a rare blepharophimosis, ptosis, and epicanthus inversus syndrome family

IntroductionBlepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic disease with diverse ocular malformations. This study aimed to investigate the disease-causing gene in members of a BPES pedigree presenting with the rare features of anisometropia, unilateral pathologic myopia (PM), and congenital cataracts.MethodsThe related BPES patients underwent a comprehensive ocular examination. Next, whole-exome sequencing (WES) was performed to screen for the disease-causing genetic variants. A step-wise variant filtering was performed to select candidate variants combined with the annotation of the variant's pathogenicity, which was assessed using several bioinformatic approaches. Co-segregation analysis and Sanger sequencing were then conducted to validate the candidate variant.ResultsThe variant c.672_701dup in FOXL2 was identified to be the disease-causing variant in this rare BPES family. Combined with clinical manifestations, the two affected individuals were diagnosed with type II BPES.ConclusionThis study uncovered the variant c.672_701dup in FOXL2 as a disease causal variant in a rare-presenting BPES family with anisometropia, unilateral pathogenic myopia, and/or congenital cataracts, thus expanding the phenotypic spectrum of FOXL2.

Prognostic Impact of Mucinous Adenocarcinoma in Stage II and III Colon Cancer.

Mucinous adenocarcinoma is a rare histologic feature of colorectal cancer and is characterized by oncologic features that are different from those of adenocarcinoma. However, there are conflicting views regarding the prognostic impact of mucinous adenocarcinoma on colon cancer. This study aimed to evaluate the prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer. This was a retrospective cohort study. This study was conducted between January 2010 and December 2015. Patients were divided into the mucinous adenocarcinoma and nonmucinous adenocarcinoma groups. Disease-free survival and overall survival were assessed using propensity score matching. Overall, 2532 patients who underwent radical surgery for stage II and III colon cancer were included in the study. The main outcome measures were disease-free survival and overall survival. The median follow-up duration was 86 months. The disease-free survival and overall survival were significantly lower in the mucinous adenocarcinoma group than in the nonmucinous adenocarcinoma group. In subgroup analysis, there was no significant difference in the disease-free survival and overall survival between patients with and without mucinous adenocarcinoma with stage II colon cancer. In stage III colon cancer, the disease-free survival and overall survival were significantly lower in patients with mucinous adenocarcinoma than in those without mucinous adenocarcinoma. Multivariable analysis showed that mucinous adenocarcinoma was a poor prognostic factor for disease-free survival and overall survival. The study's limitations include those that are inherently associated with retrospective single-center studies. Mucinous adenocarcinoma is a poor prognostic factor in stage III but not in stage II colon cancer. Therefore, mucinous adenocarcinoma might not be regarded as an independent risk factor requiring chemotherapy for favorable oncologic outcomes. However, for stage III colon cancer, patients with mucinous adenocarcinoma require close observation. ANTECEDENTES:El adenocarcinoma mucinoso es una característica histológica rara del cáncer colorrectal, se caracteriza por propiedades oncológicas que son diferentes a las del adenocarcinoma. Sin embargo, existen puntos de vista contradictorios con respecto al impacto pronóstico del adenocarcinoma mucinoso en el cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar el impacto pronóstico del adenocarcinoma mucinoso en las etapas II y III de cáncer de cólon.DISEÑO Y CONFIGURACIONES:Este estudio de cohorte retrospectivo se realizó entre enero de 2010 y diciembre de 2015. Los pacientes se dividieron entre grupos de adenocarcinoma mucinoso y adenocarcinoma no mucinoso. La supervivencia libre de enfermedad y la supervivencia global se evaluaron utilizando emparejamiento por puntuación de propensión.PACIENTES:En general, 2,532 pacientes que se sometieron a cirugía radical para etapa II y III de cáncer de colon se incluyeron en el estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana de duración del seguimiento fue de 86 meses. La supervivencia libre de enfermedad y la supervivencia global fueron significativamente menores en el grupo de adenocarcinoma mucinoso que en el grupo de adenocarcinoma no mucinoso. En el análisis de subgrupos, no hubo diferencias significativas en la supervivencia libre de enfermedad y la supervivencia global entre los pacientes con o sin adenocarcinoma mucinoso con cáncer de cólon etapa II. En el cáncer de colon etapa III, la supervivencia libre de enfermedad y la supervivencia global fueron significativamente más bajas en pacientes con adenocarcinoma mucinoso que en aquellos sin adenocarcinoma mucinoso. El análisis multivariable mostró que el adenocarcinoma mucinoso era un factor de mal pronóstico para la supervivencia libre de enfermedad y la supervivencia global.LIMITACIONES:Las limitaciones del estudio incluyen aquellas que están inherentemente asociadas con estudios retrospectivos de un solo centro.CONCLUSIONES:El adenocarcinoma mucinoso es un factor de mal pronóstico en el cáncer de colon etapa III pero no en etapa II. Por lo tanto, el adenocarcinoma mucinoso podría no considerarse un factor de riesgo independiente que requiera quimioterapia para obtener resultados oncológicos favorables. Sin embargo, para el cáncer de colon etapa III, los pacientes con adenocarcinoma mucinoso requieren observación cercana. (Traducción-Dr. Aurian Garcia Gonzalez ).

Karadeniz Alplerinin Doğal Mirasları: Ağaçbaşı, Barma ve Yılantaş Yüksek RakımTurbalıklar, Tabiatı Koruma Alanları, Trabzon, Türkiye

Turkiye's largest high plateau peatlands, Trabzon peatlands are located in the Northeast part of Turkey, on the ridges and slopes of the hills of the Soğanlı Mountains which is one of the southwestern Caucasian mountain ranges. Within the scope of this study, the geographical, climatic and ecological characteristics that provide the formation of peatlands and make the protection of peatlands important have been determined and examined. The mountainous region's climate is subtropical-Subpolar, with humid-cold climate characteristics and receives a high level of precipitation (nearly 2000 mm/y). Ağaçbaşı and Barma are the largest high plateau peatlands in the region and Turkey, one of the important natural heritage on a global scale due to their location and ecological features on the southern border of the northern hemisphere. Peatlands thicknesses vary from 50-450cm. In the region nearly 200ha of peatland-covered areas are. High plateau peatlands have ombrotrophic characteristics in which water and plant nutrients are provided only by precipitations for forming the swamps, there is no water inlet from the outside, such as streams, etc. Peatlands formed during the Holocene period after the last ice age, and have a rich archive in terms of about 8-10 thousand years old ecological and climatological data. They have several flora and fauna species that are extremely rare in Türkiye. Ağaçbaşı (2019), Barma (2019) and Yılantaş (2023) plateaus, which include peatlands, have been registered as protected natural sites and 2561Ha are taken under protection. Due to rare features, peatlands protection should be made sustainable with absolute public-state cooperation.

A rare lentiform fork sign in a patient with methanol intoxication with neurological sequelae of parkinsonism and cognitive dysfunction: A case report and literature review

Methanol intoxication is rare in developed countries. Early identification and elimination of the methanol metabolites are vital to an optimal prognosis. A characteristic brain imaging finding is bilateral basal ganglia necrosis and subcortical white matter changes. Here, we report a rare neuroradiological feature called the lentiform fork sign in a patient with methanol intoxication who survived the acute poisoning stage. We report a 31-year-old woman who presented to the emergency department with acute-onset incoherent speech, consciousness disturbance, and a high-anion-gap metabolic acidosis caused by methanol intoxication. She was treated with antidote administration of fomepizole and enhanced methanol elimination through hemodialysis. Neurological sequelae of cognitive decline and parkinsonism developed, with preserved vision. Brain MRI showed bilateral putaminal necrosis and subcortical white matter changes. The apparent diffusion coefficient map showed low signal intensities in the putamen and globus pallidus bilaterally, with brightly hyperintense rims surrounding both putamina that resembled a fork, indicating a lentiform fork sign. She then had sequelae of cognitive decline and delayed parkinsonism feature, which are compatible with the brain lesions on neuroimage studies. Methanol poisoning is an uncommon life-threatening event, and neurological sequelae result from the accumulation of formic acid, a methanol metabolite that inhibits cytochrome c oxidase in mitochondria, leading to neuronal injury. Methanol intoxication should be considered in patients with imaging findings of bilateral basal ganglia necrosis with lentiform fork sign and a metabolic acidosis of unknown origin.

Myasthenia gravis patients exhibiting an eyelid myotonia-like phenomenon

We report here a retrospective case series of 3 MG patients suffering from difficulty opening eyes that appeared together with a diagnosis of MG. All are male patients with late-onset MG who are seropositive for anti-acetylcholine receptor antibodies. The phenomenon was characterized by difficulty opening the eyes after forced closure or reflex eye closure, improving with the ice pack test and with repeated forced eye closure but worsening with pyridostigmine treatment. We provide a detailed clinical, serological, imaging and electrophysiological examination of these patients. Electromyography evaluation did not show spontaneous muscle activity or myotonia at rest in the orbital part of the orbicularis oculi muscle. However, there was sustained muscle activity lasting several seconds in the pre-tarsal and pre-septal parts of this muscle. Videos of those reported symptoms were produced and provided. We discuss the possible neurological pathophysiology of this disorder and suggest to name this rare ocular disorder “myotonia-like disorder of the pre-tarsal and pre-septal parts of the orbicularis oculi”. This study expands our knowledge of this rare clinical feature of MG and highlights the need for increased awareness of it and further investigation of this ocular manifestation.

Characteristics of a Large, Labeled Data Set for the Training of Artificial Intelligence for Glaucoma Screening with Fundus Photographs.

Significant visual impairment due to glaucoma is largely caused by the disease being detected too late. To build a labeled data set for training artificial intelligence (AI) algorithms for glaucoma screening by fundus photography, to assess the accuracy of the graders, and to characterize the features of all eyes with referable glaucoma (RG). Cross-sectional study. Color fundus photographs (CFPs) of 113 893 eyes of 60 357 individuals were obtained from EyePACS, California, United States, from a population screening program for diabetic retinopathy. Carefully selected graders (ophthalmologists and optometrists) graded the images. To qualify, they had to pass the European Optic Disc Assessment Trial optic disc assessment with ≥ 85% accuracy and 92% specificity. Of 90 candidates, 30 passed. Each image of the EyePACS set was then scored by varying random pairs of graders as "RG," "no referable glaucoma (NRG)," or "ungradable (UG)." In case of disagreement, a glaucoma specialist made the final grading. Referable glaucoma was scored if visual field damage was expected. In case of RG, graders were instructed to mark up to 10 relevant glaucomatous features. Qualitative features in eyes with RG. The performance of each grader was monitored; if the sensitivity and specificity dropped below 80% and 95%, respectively (the final grade served as reference), they exited the study and their gradings were redone by other graders. In all, 20 graders qualified; their mean sensitivity and specificity (standard deviation [SD]) were 85.6% (5.7) and 96.1% (2.8), respectively. The 2 graders agreed in 92.45% of the images (Gwet's AC2, expressing the inter-rater reliability, was 0.917). Of all gradings, the sensitivity and specificity (95% confidence interval) were 86.0 (85.2-86.7)% and 96.4 (96.3-96.5)%, respectively. Of all gradable eyes (n= 111 183; 97.62%) the prevalence of RG was 4.38%. The most common features of RG were the appearance of the neuroretinal rim (NRR) inferiorly and superiorly. A large data set of CFPs was put together of sufficient quality to develop AI screening solutions for glaucoma. The most common features of RG were the appearance of the NRR inferiorly and superiorly. Disc hemorrhages were a rare feature of RG. Proprietary or commercial disclosure may be found after the references.

Three amazing new species of the genus Chrysolina (Coleoptera: Chrysomelidae: Chrysomelinae) from China

Three new species of the genus Chrysolina Motschulsky, 1860, namely Сh. caspari sp. n., Ch. melchiori sp. n., and Ch. balthazari sp. n. are described from Sichuan and Yunnan Provinces of China. These species have rare or unique features. In Ch. caspari sp. n. the shape of the last maxillary palpomere (it is shorter and narrower than the penultimate one) is a rare case in the genus Chrysolina. Among Chinese species, this shape of maxillary palpi is known only in one species, Ch. pieli Chen, 1936. In Ch. melchiori sp. n. the relief of elytral surface (strongly reticulated irregular funnels bearing a puncture at the bottom, separated by smooth intervals) is unique for the genus Chrysolina. In Ch. balthazari sp. n. the relief of elytra (alternation of wide convex intervals between pairs of rows and very narrow flat or slightly convex intervals between rows of one pair) is well distinguishable from most Chrysolina members. Due to this feature, the new species can only be close to Ch. jinxiaoae Ge in: Daccordi, Ge, Cui, Yang, 2011 from North Sichuan. Photographs of habitus, external characters, and male aedeagi are presented.

Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane.

Wilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition. A total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated. We identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study. Our work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.

A homozygous missense variant in the PLCB4 gene causes severe phenotype of auriculocondylar syndrome type 2.

Auriculocondylar syndrome (ARCND) is a rare craniofacial birth defect characterized by malformations in the mandible and external ear (Question Mark Ear). Genetically, three distinct subtypes of ARCND (ARCND1, ARCND2, and ARCND3) have been identified. ARCND2 is linked to pathogenic variants in the PLCB4 gene (phospholipase C β4). PLCB4 is a key effector of the EDN1-EDNRA pathway involved in craniofacial development via the induction, migration, and maintenance of neural crest cells. ARCND2 is typically inherited in an autosomal dominant pattern, with recessive inheritance pattern being rare. In this study, we report the first homozygous missense variant (NM_000933.4: c.2050G>A: p.(Gly684Arg)) in the PLCB4 gene causing ARCND in a 3-year-old patient with a severe clinical phenotype of the syndrome. The patient presented with typical craniofacial ARCND features, in addition to intestinal transit defect, macropenis, and hearing loss. These findings further delineate the phenotypic spectrum of ARCND associated with autosomal recessive PLCB4 loss of function variants. Notably, our results provide further evidence that these variants can result in a more severe and diverse manifestations of the syndrome. Clinicians should consider the rare features of this condition for better management of patients.

Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene.

Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. Trio whole-exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.