The Microstructure and Mechanical Properties of Si3N4f/BN/SiBCN Microcomposites Fabricated by the PIP Process.

SiBCN ceramics based on SiC, BN and Si3N4 structures have good comprehensive properties such as high-temperature resistance, oxidation resistance, creep resistance and long life, which makes it one of the very promising ceramic material systems in military and aerospace fields, etc. In this study, SiBCN ceramics, as well as Si3N4f/BN/SiBCN microcomposites, were prepared by a polymer infiltration pyrolysis method using PBSZ as the polymer precursor. The PBSZ was completely ceramized by pyrolysis at 900 °C. The weight loss and elemental bonding forms of the products after the pyrolysis of the precursors hardly changed from 600 °C to 900 °C. After pyrolysis at 600 °C for 4 h and using the BN coating obtained from twice deposition as the interfacial phase, a more desirable weak interface of fiber/matrix with a binding strength of 21.96 ± 2.01 MPa can be obtained. Si3N4f/BN/SiBCN ceramic matrix microcomposites prepared under the same pyrolysis conditions have a relatively good tensile strength of 111.10 MPa while retaining a weak interface between the fibers and the matrix. The results of the study provide more theoretical and methodological support for the application of new composite structural ceramic material systems.

Identification of a pathogenic SMCHD1 variant in a Chinese patient with bosma arhinia microphthalmia syndrome: a case report.

BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. CASE PRESENTATION: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. CONCLUSION: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Ammonium Ion-Pre-Intercalated MnO2 on Carbon Cloth for High-Energy Density Asymmetric Supercapacitors.

With the continuous development of green energy, society is increasingly demanding advanced energy storage devices. Manganese-based asymmetric supercapacitors (ASCs) can deliver high energy density while possessing high power density. However, the structural instability hampers the wider application of manganese dioxide in ASCs. A novel MnO2-based electrode material was designed in this study. We synthesized a MnO2/carbon cloth electrode, CC@NMO, with NH4+ ion pre-intercalation through a one-step hydrothermal method. The pre-intercalation of NH4+ stabilizes the MnO2 interlayer structure, expanding the electrode stable working potential window to 0-1.1 V and achieving a remarkable mass specific capacitance of 181.4 F g-1. Furthermore, the ASC device fabricated using the CC@NMO electrode and activated carbon electrode exhibits excellent electrochemical properties. The CC@NMO//AC achieves a high energy density of 63.49 Wh kg-1 and a power density of 949.8 W kg-1. Even after cycling 10,000 times at 10 A g-1, the device retains 81.2% of its capacitance. This work sheds new light on manganese dioxide-based asymmetric supercapacitors and represents a significant contribution for future research on them.

Treatment of Cd(â ¡) and As(â ¤) co-contamination in aqueous environment by steel slag-biochar composites and its mechanism.

As toxic elements of concern, Cd(II) and As(V) pose a threat to human health. In this study, a new type of magnetic adsorbent (SBNa800) was prepared using a mixture of industrial waste steel slag and ginkgo leaves to treat wastewater contaminated with Cd(II) and As(V). The maximum adsorption capacities of SBNa800 for Cd(II) and As(V) were 109.17 (pH 5, 1.82 times that of the original biochar) and 59.79 (pH 3) mg/g, respectively. Cd(II) and As(V) adsorption capacities was above 90 % at pH = 4. Cd(II) and As(V) were synergistic and competitive adsorption. The results of µ-XRF, XANES and XPS showed that Cd(II) was adsorbed by SBNa800 in the forms of Cd(OH)2, CdCO3, Cd5H2(AsO4)4·4 H2O, CdCl2·2.5 H2O and Cd(NO3)2. About 52.79-64.61 % As(V) was reduced to As(III) by Fe(0) on SBNa800 and then adsorbed. The adsorption mechanisms of Cd(II), As(V) and As(III) were hydrogen bonding/electrostatic attraction, inner-sphere complexation and precipitation. The saturation magnetisation of SBNa800, which was easy to separate from wastewater, was 6.54 emu/g. Therefore, SBNa800 can be used as a potential adsorbent to treat wastewater contaminated with Cd(II) and As(V).

Clinical evaluation of fenestration decompression combined with secondary curettage for ameloblastoma of the jaw: retrospective radiographic analysis.

BACKGROUND: Ameloblastoma is a benign odontogenic epithelial tumor with local infiltration and a high recurrence rate that occurs most frequently in the jawbone. The aim of this study was to investigate the outcomes of fenestration decompression combined with secondary curettage (FDSC) in the surgical treatment of jaw ameloblastoma, and clarify the possibility of FDSC to become an appropriate therapeutic method for ameloblastoma with large lesion. METHODS: A retrospective analysis was carried out in 145 patients diagnosed with multicystic ameloblastoma (MA) and 88 patients with unicystic ameloblastoma (UA). These patients were divided into two groups based on the therapeutic regimen: the FDSC group and the local curettage (LC) group. Panoramic radiography was taken 2 years after curettage to evaluate the change in lesion area in each case, and the therapeutic effects of different treatment methods were further assessed by the chi square test. RESULTS: For MA, the effective rate of cystic cavity area reduction in the FDSC group (71.19%) was higher than that in the LC group (30.23%) (P < 0.001). For UA patients, the effective rate of lesion area reduction after FDSC was 93.02%, which was higher than that after LC (53.33%) (P < 0.001). Moreover, the recurrence rate of the FDSC group in the MA was 30.51%, which was significantly different from that of the LC group (P < 0.001). Regarding UA, the recurrence rates were 13.95% and 28.89%, after FDSC and LC, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSIONS: FDSC exhibits a much better curative effect than LC in both MA and UA, whereas the recurrence rate of these two therapeutic strategies did not significantly differ in UA. The above data demonstrated that FDSC may serve as a routine, safe, effective and appropriate surgical treatment plan for MA or UA patients with large lesions.

A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient.

Heterotaxy syndrome is a very rare congenital disease, which is caused by the disorder of left-right asymmetry during visceral development. However, pathogenic genetic lesions are found in less than 20% of HS patients. In this cohort study, whole-exome sequencing was performed for 110 patients with situs inversus or situs ambiguous. We identified a novel nonsense variant in PKD1L1(c.1387 C > T; p.463Gln*) in a Chinese patient with heterotaxy syndrome and congenital asplenia. This homozygous variant caused the domain of PKD1L1 complete absence. To our knowledge, this novel variant is the first phenotype of congenital asplenia found in patients with PKD1L1 variants, and the first PKD1L1 variant found in China. Our findings expand the spectrum of PKD1L1 variants and provide support for PKD1L1 variant and congenital asplenia, and the critical role of PKD1L1 during left-right patterning in the Han Chinese population.

[Treatment of maxillary ameloblastoma with different modalities: a retrospective analysis of 92 cases].

PURPOSE: To explore the appropriate surgical approach for each type of maxillary ameloblastoma. METHODS: The clinical data of 92 patients with maxillary ameloblastoma were retrospectively analyzed. All patients were pathologically diagnosed, followed up for 3-8 years after surgery, maxillofacial CT and panoramic images were taken regularly to observe the surgical outcomes. SPSS 22.0 software package was used for data analysis. RESULTS: The proportion of maxillary ameloblastoma in male and female patients was 3 to 1,with more male patients and the mean age was 45.77 years old. The total recurrence rate of 92 patients was 21.74%, among which unicystic ameloblastoma had no recurrence after different surgical procedures. Among 38 patients with typical maxillary ameloblastoma, 14 underwent curettage, 3 underwent decompression，16 underwent extended resection, 3 underwent subtotal maxillary resection, 1 underwent iliac bone transplantation after subtotal maxillary resection, and 1 underwent reconstruction with anterolateral thigh flap after subtotal maxillary resection. Among them, 18 had recurrence and 5 had canceration. Three patients with extrasseous/peripheral type underwent expanded resection and two underwent curettage，none of them had recurrence. One patient with metastasizing ameloblastoma recurred after extended resection. CONCLUSIONS: Maxillary ameloblastoma with unicystic type should be completely removed with minimal trauma. The recurrence rate of maxillary ameloblastoma via simple curettage or extended resection is still relatively high, which may be due to the large tumor involvement scope of these patients and the failure of complete tumor removal by curettage. For external/peripheral ameloblastoma and metastatic ameloblastoma, the involved jaw bone should be removed as much as possible to prevent recurrence. For malignant transformation of ameloblastoma, the tumor and jaw bone should be dissected during the operation to reduce recurrence rate. The primary site, cervical lymph nodes and lungs should be closely followed after operation to detect early metastasis.

Knee Scores of Patients with Non-Lateral Compartmental Knee Osteoarthritis Undergoing Mobile, Fixed-Bearing Unicompartmental Knee and Total Knee Arthroplasties: A Randomized Controlled Trial.

OBJECTIVE: To evaluate knee scores and clinical efficacies of patients with non-lateral unicompartmental knee osteoarthritis (OA) who randomly underwent mobile-bearing (MB) unicompartmental knee arthroplasty (UKA), fixed-bearing (FB) UKA, and total knee arthroplasty (TKA). METHODS: From September 2015 to February 2017, a prospective, randomized, parallel, single-center trial of 180 patients (78 males and 102 females; 63.3 ± 6.9 years) with non-lateral compartmental knee OA was performed in the first author-affiliated hospital. The patients were randomly divided into three groups (each group included 60 patients) and received medial cemented Oxford phase 3 MB UKA, medial cemented Link FB UKA, or cemented DePuy Sigma PFC TKA, respectively. A similar perioperative management and fast-track surgery program was carried out for all patients. The knee scores at 3-year follow-up after operation and clinical efficacies of these three groups of patients were recorded, investigated, and compared. RESULTS: Primarily, compared to the TKA group, the UKA groups (MB UKA and FB UKA) had shorter operative time (median 63.2 < 67.1 min), less bleeding (8.6 < 30.0 mL), earlier resumption of walking without crutches (3.0 < 8.0 days) and walking up and down the stairs (5.0 < 10.0 days) (P < 0.001), higher FJS scores (78.0 > 74.5) (P = 0.007), better results in all knee scores (except VAS and KSS function scores) (P < 0.05), and a larger maximum flexion angle of the knee at the 3-year follow-up (123.0° > 96.0°) (P = 0.001). Secondarily, compared to the TKA group, the MB UKA group showed better results in the Western Ontario and McMaster Universities index (WOMAC) stiffness (83.6 > 79.6), WOMAC total (86.3 > 83.2), Oxford knee score (OKS) (20.0 < 23.0), Forgotten Joint Score (FJS) (78.5 > 74.5), and a larger maximum flexion angle of the knee (123.0 > 96.0) (P < 0.05). Moreover, the FB UKA group showed higher Hospital for Special Surgery Knee Score (HSS) (91.0 > 88.5), WOMAC stiffness (84.3 > 79.6), WOMAC function (85.2 > 81.7), WOMAC total scores (87.6 > 83.2), and a larger maximum flexion angle of the knee (119.0° > 96.0°) than the TKA group (P < 0.05). Overall, there was no significant difference in all knee scores and maximum flexion angles of the knee for the MB UKA and FB UKA groups (P > 0.05). There was one case with original bearing dislocation in MB UKA group. One patient with displacement of the femoral component caused by a fall injury, and another patient, who lost his life in a car accident, were involved in the FB UKA group. There was an infection case and an intermuscular vein thrombosis case in TKA group. CONCLUSION: UKA showed more advantages than TKA; however, there was no significant difference between the MB UKA and FB UKA groups for treatment of non-lateral compartmental knee OA.

A New Three-Dimensional Classification of Proximal Tibiofibular Fractures: A Multicenter Study.

OBJECTIVES: To propose an updated definition of proximal tibia and fibula fracture (PTFF) and establish a three-dimensional (3D) structure-based classification of PTFF. METHODS: In total, 1358 adult patients (837 males and 521 females; 43.61 ± 15.13 years， 1364 affected knees) who were diagnosed with PTFF at the departments of orthopaedic surgery of four hospitals from January 2010 to December 2019 were enrolled. The new classification of PTFF, termed Wu classification, included three parts: classification of columns in the horizontal plane, regions in the frontal plane, and segments in the sagittal plane. All PTFFs were classified according to Schatzker, Luo, and Wu classification systems. Additionally, the incidence and characteristics of PTFFs were analyzed. RESULTS: The major internal structural fractures of PTFF were tibial plateau fracture (TPF) only (725, 53.15%), TPF and proximal fibular fracture (274, 20.09%), and isolated avulsion fracture of the posterior cruciate ligament (PCL) (189, 13.86%). Approximately a quarter of PTFF cases could not be classified using Schatzker or Luo classifications, but all PTFF cases could be classified using Wu classification. The most frequent PTFFs included all four columns in region IV, segment 2 (235, 17.23%); the posterolateral and posteromedial columns in region II, segment 2 (191, 14.00%); and the lateral and posterolateral columns in region IV, segment 2 (136, 9.97%). Isolated avulsion fracture of the anterior cruciate ligament (ACL) was categorized as three injury types, most of which involved the lateral and medial columns in region II, segment 1 (40/63, 64%). More than 97% of cases of isolated fractures of the PCL involved the posterolateral and posteromedial columns in region II, segment 2. The most frequent combined avulsion fracture of the ACL and PCL included all four columns in region II, segment 2 (18/24, 75%). All of the isolated avulsion fractures of the ACL were located in segment 1, and all those of the PCL in segment 2. The most common type of isolated proximal fibular fracture involved the posterolateral column in region III, segment 2 (23/26, 88%). The most frequent combined TPF and proximal fibular fracture involved all four columns in region IV, segment 2 (107/274, 39.05%). CONCLUSIONS: All cases of PTFF could be classified by the new 3D Wu classification which should be beneficial for clinical diagnosis, guidance of treatment, statistical analysis, academic communication, and prognosis, and the most frequent PTFF involved all four columns in region IV, segment 2.

Case Report: BAF-Opathies/SSRIDDs Due to a de novo ACTL6A Variant, Previously Considered to Be Heart-Hand Syndrome.

Purpose: This study aims to identify genetic lesions in patients with congenital heart disease (CHD) with or without other phenotypes. In this study, over 400 patients were recruited and several novel variants in known causative genes were identified. A Chinese patient clinically diagnosed with HHS (patent ductus arteriosus, persistent left superior vena cava, and congenital absence of left arm radius) was included in the study cohort. Methods: Targeted, whole exome, and Sanger sequencing were performed to identify genetic lesions. The effects of the variant on ACTL6A RNA and protein were assessed using bioinformatics analysis. Results: At the start of the study, no mutations in known and candidate causative genes associated with CHD were identified. Seven years later, we noticed craniofacial deformities and identified a de novo heterozygous deletion variant in ACTL6A (NM_004301, c.478_478delT; p.F160Lfs*9). Intellectual disability and short stature were identified by a follow-up visit 10 years later. This variant leads to frameshift sequences and a premature termination codon and may affect the features of proteins. According to the nonsense-mediated mRNA decay theory, this variant may induce the decay of ACTL6A mRNA in patients. Conclusion: Our study reported the first ACTL6A variant in a Chinese individual, providing further evidence that ACTL6A is involved in heart and upper limb skeletal and intellectual development, thereby expanding the spectrum of ACTL6A variants. Thus, mutation analysis of the ACTL6A gene should be considered in patients with BAF-opathies or heart-hand syndromes due to potential misdiagnosis. Craniofacial dysmorphisms and intellectual disability are key to distinguishing these two diseases clinically, and attention to developmental delay/intellectual disability and craniofacial deformities will contribute to the diagnosis of BAF-opathies.

A novel POF1B variant in a Chinese patient is associated with premature ovarian failure.

A novel mutation of POF1B was identified in a patient with premature ovarian failure.

Case Report: Mutant SCN9A Susceptible to Charcot Neuroarthropathy in a Patient With Congenital Insensitivity to Pain.

Charcot neuroarthropathy is a systemic disease with pathological changes in the musculoskeletal system, which leads to fractures, dislocations, and deformities involving multiple bones and joints, particularly those of the feet. While the common underlying cause of Charcot neuroarthropathy is diabetes mellitus, it is also associated with congenital insensitivity to pain (CIP). CIP is a rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. In this study, we report a patient with CIP from a consanguineous family susceptible to Charcot neuroarthropathy with a novel SCN9A mutation. This report involves the case of a middle-aged man who suffered from CIP, had repeated painless fractures, and developed bone and joint destruction. The physical and radiological examinations revealed that multiple joints were swollen and deformed, and soft-tissue trauma was evident. We identified a novel homozygous SCN9A mutation (p.Cys1339Arg) by whole-exome sequencing (WES), which was verified using Sanger sequencing. In addition, the wild-type (WT) and mutated p. Cys1339Arg were assessed in HEK293 cells expressing Nav1.7, and the results showed that p. Cys1339Arg almost abolished the Nav1.7 sodium current. In conclusion, Charcot neuroarthropathy associated with CIP demonstrated a wider spectrum of Charcot neuroarthropathy than was previously recognized or documented. In addition, this finding is conducive to understanding the critical amino acids for maintaining the function of Nav1.7, thus contributing to the development of Nav1.7-targeted analgesics.

[Efficacy of intramedullary nail fixation for the tretament of tibial shaft fracture with difference approachs].

OBJECTIVE: To compare clinical effect of intramedullary nailing through suprapatellar, infrapatellar and paracpatellar approach in treating tibial shaft fracture. METHODS: From June 2012 to June 2018, 36 patients with tibial shaft fracture were treated with intramedullary nails, and were divided into three groups according to surgical approach. Twleve patients were through suprapatellar approach, including 7 males and 5 females aged from 25 to 53 years old with an average of (37.8±11.4) years old;and 4 patients were type A, 4 patients were type B, and 4 patients were type C according to AO classification. Ten patients were through infrapatellar approach, including 6 males and 4 females aged from 19 to 56 years old with an average of (35.6±10.0) years old;and 3 patients were type A, 4 patients were type B, and 3 patients were type C according to AO classification. Forteen patients were through paracpatellar approach, including 8 males and 6 females aged from 21 to 58 years old with an average of (36.6±10.0) years old;and 4 patients were type A, 6 patients were type B, and 4 patients were type C according to AO classification. Operation time, intraoperative blood loss, fluoroscopy times, fracture healing time and complications among three groups were observed, and knee joint functions were evaluated by Lysholm score. RESULTS: All patients were followed up from 12 to 18 months with an average of (15.0±3.0) months. There were no difference in intraoperative blood loss and fracture healing time among three groups (P>0.05). There were statistical difference in operation time, fluoroscopy times and complications compared with suprapatellar approach and infrapatellar approach, paracpatellar approach (P<0.05). While there were no difference in operation time, fluoroscopy times and complications between infrapatellar approach and paracpatellar approach (P>0.05). Lysholm score among suprapatellar approach, infrapatellar approach and paracpatellar approach were (87.5±7.5), (78.2±6.7) and (77.4±6.3) respectively, and had differences among three groups (P<0.05). Compared with suprapatellar approach and infrapatellar approach, paracpatellar approach, there were difference in squatting, climbing stairs, pain and total scores (P<0.05);while there were no difference between infrapatellar and paracpatellar group (P>0.05). CONCLUSION: intramedullary nailing through suprapatellar for the treatment of tibial shaft fracture is benefit for fracture healing and recovery of knee joint function, while infrapatellar and paracpatellar approach have advantages in exposure of insertion point. We should select approach reasonably according to our experience.

A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

[Expression and clinical significance of HIST1H2BH in head and neck squamous cell carcinoma].

PURPOSE: The purpose of this study was to investigate the expression of HIST1H2BH in head and neck squamous cell carcinoma (HNSCC) and to analyze its clinical significance. METHODS: The expression of HIST1H2BH in different tumors and HNSCC were analyzed based on the Oncomine and GEPIA database, and its relationship with clinicopathological parameters and prognostic value of HNSCC patients were also analyzed. The expression of HIST1H2BH in clinical specimens were detected by immunohistochemical staining. The variation of HIST1H2BH in HNSCC and its relationship with prognosis were analyzed based on the cBioPortal database. The interaction proteins and molecular mechanism of HIST1H2BH were preliminarily predicted using the String database. SPSS 24.0 software package was used for statistical analysis of the data. RESULTS: Analysis of Oncomine database and GEPIA database showed that HIST1H2BH was highly expressed in variety of tumors, and was significantly highly expressed in HNSCC. The expression level of HIST1H2BH was closely related to the pathological stage and prognosis of HNSCC patients, the prognosis of patients with high HIST1H2BH expression was poor. Immunohistochemical results of clinical specimens showed that the expression of HIST1H2BH in the cancerous tissue of HNSCC patients was significantly higher than that in the adjacent tissues. cBioPortal database analysis showed that the variation rate of HIST1H2BH in HNSCC patients was not high, but it was related to the disease-free survival rate. String database analysis showed that there were many genes associated with HIST1H2BH, and the signal pathways involved in biological processes were also complex. CONCLUSIONS: The expression of HIST1H2BH is elevated in HNSCC tissues, and its high expression is associated with poor prognosis. HIST1H2BH could be served as a marker for diagnosis and prognosis of HNSCC.

A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient.

The position and morphology of human internal organs are asymmetrically distributed along the left-right axis. Aberrant left-right patterning in the developing embryo can lead to a series of congenital laterality defects, such as dextrocardia and heterotaxy syndrome. Laterality defects are a genetic condition; however, pathogenic genetic lesions are found in only one-fifth of patients. In this study, whole-exome sequencing was conducted for 78 patients with laterality defects. We identified a novel stopgain variant in MMP21 (c.G496T; p.G166*) in a Chinese patient with mirror-image dextrocardia. This variant caused a truncated MMP21 mRNA containing only the signal peptide and propeptide, while the coding sequence of matrix metalloproteinase-21 was almost entirely absent. To the best of our knowledge, this novel variant is the first homozygous stopgain variant identified in dextrocardia patients, and the first MMP21 variant found in East Asia. Our findings expand the spectrum of MMP21 variants and provide support for the critical role of MMP21 during left-right patterning in the Han Chinese population.

Novel Compound Heterozygous DST Variants Causing Hereditary Sensory and Autonomic Neuropathies VI in Twins of a Chinese Family.

Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.

Identification of an unknown frameshift variant of NOG in a Han Chinese family with proximal symphalangism.

Proximal symphalangism (SYM1) is an autosomal dominant disorder manifested by ankylosis of the proximal interphalangeal joints of fingers, carpal and tarsal bone fusion, and conductive hearing loss in some cases. Herein, we clinically diagnosed a Chinese patient with fusions of the bilateral proximal interphalangeal joints in the 2-5 digits without conductive hearing loss. Family history investigation revealed that his mother and grandfather also suffered from SYM1. Whole exome sequencing was performed to detect the genetic lesion of the family. The candidate gene variants were validated by Sanger sequencing. By data filtering, co-segregation analysis and bioinformatics analysis, we highly suspected that an unknown heterozygous frameshift variant (c.635_636insG, p.Q213Pfs*57) in NOG was responsible for the SYM1 in the family. This variant was predicted to be deleterious and resulted in a prolonged protein. This finding broadened the spectrum of NOG mutations associated with SYM1 and contributed to genetic diagnosis and counseling of families with SYM1.