Improving the Anti-washout Property of Acrylate Grouting Material by Bentonite: Its Characterization, Improving Mechanism, and Practical Application.

Acrylate is a popular polymer grouting material that has been widely used to control groundwater seepage. However, the vulnerability of acrylate slurry to dynamic water washout restricts its application in groundwater environments characterized by high flow velocity and water pressures. In this paper, lithium bentonite (Li-B) was used to modify the traditional magnesium acrylate (AC) grouting material. The influence of Li-B to AC ratios on the modified materials' washout resistance was explored, and the modification mechanism was analyzed using X-ray diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM). Finally, the anti-washout ability of the modified slurry was verified through engineering applications. Results revealed that LiB-AC grout had adjustable setting times (10.5 to 395.6 s), minimal bleeding (0.1%), higher viscosity (65 mPa·s) and expansibility (350%), stronger anti-water dispersibility (24 times that of pure AC slurry), higher mechanical strength (compressive strength is 0.386 MPa, tensile strength is 0.088 MPa), and better impermeability (2.23 × 10-8 m/s). The lithium bentonite was beneficial to the setting time, bleeding, viscosity, slurry retention rate, impermeability, and mechanical strength of the acrylate grout. However, it diminished the expansibility of the acrylate grout. At the optimal acrylate content (20%), the mechanical strength and impermeability of the LiB-AC grout were the highest. The better performance of LiB-AC grout was attributed to the formation of a more stable and dense interlaced spatial network structure after the modification by Li-B. The LiB-AC grout was used in the dynamic water grouting project of a metro shield tunnel segment and achieved better anti-washout performance than cement-water glass and pure AC slurry.

Factors affecting soil treatment with the microbially induced carbonate precipitation technique and its optimization.

The microbially induced carbonate precipitation (MICP) technique has been used to increase mechanical strength, reduce permeability, and fix radionuclides of soils, etc. To achieve effective soil cementation by MICP, 3 aspects should be considered: MICP efficiency, bacterium retention (in soils after injections), and precipitation uniformity. Here, experiments and statistical analyses were conducted to understand the parameters affecting the 3 aspects. Moreover, the parameters leading to better performance in these aspects were designed and used to conduct MICP soil cementation with varying the number of injections. The results present that temperature and OD600nm of bacterial suspension are the most important parameters affecting MICP efficiency, followed by reaction time, pH, and concentration of cementation solution, and they are all statistically significant. As these parameters increased, MICP efficiency (ratio of CaCO3 formed to Ca2+ added) first increased quickly and then slowly or decreased. The soil particle size distribution and injection rate affected bacterium retention greatly. Smaller particle sizes, wider particle-size-distribution spans, and slower injection rates are beneficial to bacterium retention. However, higher injection rates favour precipitation uniformity. Finally, the unconfined compressive strength (UCS) of the bio-treated soil can be increased further by increasing the number of injections.

Case report: Pathological and genetic features of pancreatic undifferentiated carcinoma with osteoclast-like giant cells.

Objectives: Pancreatic undifferentiated carcinoma accounts for 2%-7% of pancreatic carcinomas. We aimed to investigate the pathological and genetic characteristics of pancreatic undifferentiated carcinoma with osteoclast-like giant cells and the key points of treatment. Methods: The clinical data and follow-up results of four patients diagnosed with pancreatic undifferentiated carcinoma with osteoclast-like giant cells between May 2015 and May 2020 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed. Results: Chief complaints included "pain and discomfort in the upper abdomen" (2/4), "nausea and vomiting" (1/4) or no symptoms (1/4). Preoperative mildly elevated tumor markers included carcinoembryonic antigen (1/4) and CA19-9 (1/4). The tumors were located in the tail of the pancreas in three patients and the head and neck in one patient. Tumor metastasis was found in pancreatic adipose tissue in two patients and lymph node metastasis in one patient, with microscopic heterogeneous mononuclear cells and scattered osteoclast-like giant cells of various sizes. One patient (1/4) had a mucinous cystic tumor of the pancreas, and two patients (2/4) had adenocarcinoma of the pancreatic duct. Only one patient received postoperative gemcitabine combined with albumin-bound paclitaxel chemotherapy. Conclusion: Currently, treatment guidelines are lacking for PUC-OGC, and prognosis varies markedly. More cases must be reported to clarify its origination. The long-term follow-up of diagnosed patients and genetic mutation testing can also contribute to improving treatment and prognosis of this disease.

Effects of Enhanced Recovery Rehabilitation Surgery Concepts on the Surgical Process, Postoperative Pain, Complications, and Prognosis of Discectomy in Patients with Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study was to investigate the effect of lumbar disc herniation (LDH) disease degree on lumbar discectomy and to explore the relationship between the degree of intervertebral disc disease and postoperative pain score changes. Methods: We conducted a comprehensive search in China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, MEDLINE, Embase, Cochrane database, and other databases, obtained all relevant studies as of April 2017, and then followed strict inclusion and exclusion criteria. Standard screening was performed on the retrieved literature. We extract and analyze key data using Review Manager 5.3 software. Pooled effects were calculated by mean difference or odds ratio and 95% confidence interval analysis, depending on data attributes. Results: Various databases were searched for the results of papers from lumbar discectomy since April 2017 to April 2022. Nine papers from 2502 patients were selected. The average overall follow-up was 52 weeks. There were statistically significant reductions in postoperative pain scores and degree of disc disease. There was a significant correlation between the reduction in pain score after discectomy and the degree of disc disease (r = 0.73, 95%CI = 0.01-1.20, p = 0.005). Conclusions: Decreased disc disease grade is one of the reasons for the lower back pain score after discectomy. Furthermore, region-dependent economic factors must be considered before developing a treatment strategy. Larger, well-defined randomized controlled trials are needed to further confirm these results.

Comparative Efficacy of Three Minimally Invasive Procedures for Kümmell's Disease: A Systematic Review and Network Meta-Analysis.

Background: Percutaneous vertebroplasty (PVP), percutaneous kyphoplasty (PKP), and bone-filling mesh containers(BFC) are three viable minimally invasive techniques that have been used to treat Kümmell's disease(KD). However, there is still debate as to which is safer and more effective. This study summarized the pros and cons of the three techniques in the treatment of KD through network meta-analysis(NMA). Methods: All eligible published clinical control studies comparing PVP, PKP, and BFC for KD up to December 2021 were collected by online search of Cochrane Library, PubMed, Embase, CNKI, Wanfang Database, and Chinese biomedical literature database. Data were extracted after screening, and Stata 16.0 software was used to perform the network meta-analysis. Results: Four randomized controlled trials (RCTs) and 16 retrospective case-control studies (CCTs) with a total of 1114 patients were included. The NMA results showed no statistical difference between the 3 procedures in terms of improving patients' clinical symptoms. PKP was most likely to be the most effective in correcting kyphosis, while BFC was likely to be the most effective in managing the occurrence of cement leakage. No statistical differences were found in the incidence of new vertebral fractures in adjacent segments. Conclusions: Ranking analysis showed that BFC has the highest likelihood of being the optimal procedure for the treatment of KD, based on a combined assessment of effectiveness in improving patients' symptoms and safety in the occurrence of adverse events.

The monitoring approaches and non-destructive testing technologies for sewer pipelines.

Sewage pipe deterioration has been one of the factors causing huge asset losses and urban hazards worldwide. For more efficient and reliable management, a variety of monitoring and non-destructive testing techniques has been developed for defect inspection and condition assessment of sewer pipes. In the present paper, the monitoring approaches of sewage pipes in the form of operational monitoring, structural monitoring, and durability monitoring are outlined. The fundamentals and features of various non-destructive testing (NDT) techniques for different target detect locations are presented. The stereo vision, light detection and ranging (LiDAR), and laser 3D scanning technologies that might serve to architect the digital twin of the pipeline are also described. What's more, the capabilities and limitations of these technologies are discussed and summarized in tables. Some possible visions for the development of inspection and quantitative evaluation of sewage pipes are also discussed. In practice, it is suggested that visual inspection techniques are the most feasible for the evaluation of underground pipes. In terms of quantitative and automated evaluation, visual inspection robots equipped with stereo vision or laser 3D scanning technology are the most promising.

The Effect of Cross-Linking Type on EPDM Elastomer Dynamics and Mechanical Properties: A Molecular Dynamics Simulation Study.

The cross-linking structure of the Ethylene-propylene-diene monomer (EPDM) is made up of a number of cross-linking types, including carbon atoms from the main chain or monomer and ether crosslinks formed during degradation. Through molecular dynamic simulations, the contribution of each type of cross-linked structure to the dynamics and mechanical properties of EPDM, the study's focus, were investigated. Cross-linking between the tertiary carbons of two main chains, cross-linking at the monomer's unsaturated position, ether cross-linking after oxidation, and other combinations of target cross-linked carbon atoms from different positions, totaling eight types of cross-linked types, were mixed with EPDM free chains in a 1:1 ratio to form eight types of cross-linked EPDMs. These varieties of cross-linked EPDMs were then compared to an uncross-linked EPDM in terms of density, radius of gyration, free volume, mean square displacement, and uniaxial tensile stress-strain curves. It was found that the cross-linking was always proven to have a favorable influence on mechanical characteristics; however, the relaxation inhibition effect varied. The cross-linking between the diene monomer at the C9 position resulted in a more flexible molecular shape and was more than double the free volume of the uncross-linked EPDM, resulting in an improved diffusion ability. The ether cross-linking produced by the oxidation of the side chain cross-linking improved the positive contribution to stiffness and enhanced the inhibitory impact on diffusion properties, whereas the main chain cross-linking had the opposite effect. The research presented in this study leads to a better knowledge of the microscopic aspects underlying EPDM performance.

Clinicopathologic features of a patient with primary monophasic synovial sarcoma of the jejunum.

A case of primary synovial sarcoma of the jejunum was collected and analyzed retrospectively. A 19-year-old man who presented to hospital with abdominal pain. The CT scan showed a large mixed abdominal mass with bleeding. Laparotomy revealed that the tumor originated from the jejunum, accompanied by rupture and hemorrhage. Microscopically, the tumor was composed of spindle cells. The tumor cells demonstrated diffuse expression of vimentin, transducin-like enhancer (TLE)-1, B-cell lymphoma protein (Bcl)-2, CD99 and focal expression of epithelial membrane antigen (EMA). The presence of specific SS18 gene rearrangement was confirmed in tumor cells. The patient received 6 cycles of chemotherapy after jejunal tumor resection. And 12 months later, the patient presented pancreatic metastasis and had radiotherapy. The patient died 15 months after the diagnosis.

Prenatal ultrasound-assisted identification of multiple malformations caused by a deletion in the long-arm end of chromosome 7 and review of the literature.

Clinical cases of chromosome 7 long-arm end deletion are rare. Generally, 7q terminal deletion syndrome results in complex clinical phenotypes, such as microcephaly, growth and development retardation, holoprosencephaly, and sacral hypoplasia. Herein, we report the genetic and clinical features of a fetus with multiple malformations observed by prenatal ultrasound. The results showed that there was a large fragment deletion of approximately 27.7 Mb in 7q32.3-qter. The induced fetus showed facial abnormalities of cleft lip and palate, and some organ structural abnormalities (such as diaphragmatic hernia and polycystic renal dysplasia) were observed by autopsy and pathology. To provide more reliable information for disease diagnosis and genetic counseling, we reviewed and analyzed the reported cases of isolated 7q terminal syndrome.

Usher syndrome type 2A complicated with glycogen storage disease type 3 due to paternal uniparental isodisomy of chromosome 1 in a sporadic patient.

BACKGROUND: The condition of uniparental disomy (UPD) occurs when an individual inherits two copies of a chromosome, or part of a chromosome, from one parent. Most cases of uniparental heterodisomy (UPhD) do not cause diseases, whereas cases of uniparental isodisomy (UPiD), while rare, may be pathogenic. Theoretically, UPiD may cause rare genetic diseases in a homozygous recessive manner. METHODS: A 4-year-old girl presented with congenital hearing loss, developmental delay, hepatomegaly, and other clinical features. She and her parents were genetically tested using trio whole exome sequencing (Trio-WES) and copy number variation sequencing (CNV-seq). In addition, we built a structural model to further examine the pathogenicity of the UPiD variants. RESULTS: Trio-WES identified a paternal UPiD in chromosome 1, and two homozygous pathogenic variants AGL c.4284T>G/p.Tyr1428* and USH2A c.6528T>A/p.Tyr2176* in the UPiD region. We further analyzed the pathogenicity of these two variations. The patient was diagnosed with Usher syndrome type 2A (USH2A) and glycogen storage disease type III (GSD3). CONCLUSIONS: Our study reports a rare case of a patient carrying two pathogenic variants of different genes caused by paternal UPiD, supporting the potential application of Trio-WES in detecting and facilitating the diagnosis of UPD.

IDDCA syndrome in a Chinese infant due to GNB5 biallelic mutations.

Herein, we present a Chinese infant with an early-onset intellectual developmental disorder with cardiac arrhythmia syndrome. A 6-month-old boy visited our hospital because of convulsions and paroxysmal cyanosis for 1 day. Mental development analysis showed that the patient had a neurodevelopmental delay. Frequent seizures occurred, and ECG monitoring demonstrated severe cardiac arrhythmia. Whole-exome sequencing showed that the infant had two compound heterozygous variants, NM_016194:c.458G>A/p.Cys153Tyr and NM_016194:c.1032C>A/p.Tyr344*, in GNB5. The first variant was inherited from his mother, while the other one was a de novo variant. Haplotype analysis indicated that the de novo variant was located in the paternal chromosome. Structural modeling indicated that both mutations could influence the interaction of GNB5 with its binding protein. Our study expanded the known genetic and phenotypic spectrum of GNB5-associated diseases, by presenting a Chinese male infant with IDDCA.

Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia.

BACKGROUND: Sitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention. METHODS: We evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio-whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved. RESULTS: We identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965-1G>A, c.323-1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes. CONCLUSIONS: Our findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

Biallelic INTS1 Mutations Cause a Rare Neurodevelopmental Disorder in Two Chinese Siblings.

This study presents two Chinese siblings with a rare neurodevelopmental disorder (NDD) caused by biallelic INTS1 mutations and investigates the clinical features of this disease by means of in silico analysis. Two siblings, an 11-year-old brother and a 5-year-old sister, visited our hospital due to physical retardation and profound intellectual disability. Whole-exome sequencing (WES) was performed for the girl, and Sanger sequencing was used to validate the identified variants. Phenotype correlation analysis and in silico genetic interaction network analysis were performed to investigate genes that could lead to diseases similar to the rare disease in the patients. Growth retardation, distinct intellectual disability, hypertelorism, mild cataract, uneven teeth, abnormal palmar and plantar creases, and dubious genitalia were noted in the sister. No neurological features related to neuropathy were found. The brother showed features and growth delay similar to his sister. Heterozygous novel variants of c.1645A>G,p.Met549Val and c.5881C>T,p.Gln1961* in INTS1 were considered a candidate etiology. Sanger sequencing demonstrated that the variants were inherited from the grandfather and (maternal) grandmother. Phenotype correlation analysis revealed that CTDP1 mutation-induced congenital cataracts-facial dysmorphism-neuropathy (CCFDN) mostly overlapped with the performance of our patients. In silico analysis of the genetic interaction network showed that INTS1 is highly associated with INTS8 and CTDP1. Our study further validated that biallelic INTS1 mutations could bring about the onset of a novel neurodevelopmental disorder.

Mutation in BRAF and SMAD4 associated with resistance to neoadjuvant chemoradiation therapy in locally advanced rectal cancer.

Our study was done in order to identify novel molecular markers to predict which locally advanced rectal cancers (LARCs) might be resistant to neoadjuvant chemoradiotherapy (nCRT). Seventy-four patients with LARCs treated with nCRT were collected. Pathological evaluation after nCRT was performed according to the tumor regression grading (TRG) system. Next-generation sequencing kit including 279 exons of 59 genes was performed on Illumina Miseq Platform. Sanger sequencing was performed to confirm some mutations. Four of the tumors (4/74, 5.4%) had BRAF mutation, which presented in one TRG 2 tumor and three TRG 3 tumors but was not observed in TRG 0-1 tumors. Higher mutational frequency of BRAF gene in TRG 3 tumors (3/12, 25%) was found in comparison with the TRG 0-2 tumors (1/62, 1.6%; p = 0.012). Eight tumors (8/74, 10.8%) harbored SMAD4 mutations, which was mutated across all TRG groups. However, SMAD4 mutated more in TRG 3 tumors (4/12, 33.3%) compared with that in TRG 0-2 tumors (4/62, 6.5%; p = 0.020). The patients with BRAF-mutated LARCs had shorter progression-free survival (PFS) (p = 0.045) and shorter overall survival (OS) (p = 0.000) than the BRAF wild-type (WT) ones. The patients with SMAD4-mutated tumors had shorter PFS than the WT cases (p = 0.008). BRAF and SMAD4 genetic mutations might be important molecular markers to predict resistance to nCRT and poor prognosis in LARCs. More cases are needed to confirm these findings in the near future.

Understanding Free Volume Characteristics of Ethylene-Propylene-Diene Monomer (EPDM) through Molecular Dynamics Simulations.

Understanding the underlying processes associated with the viscoelasticity performance of ethylene-propylene-diene monomer (EPDM) during its service life is essential for assessing and predicting its waterproofing performance in underground infrastructure. The viscoelasticity of the polymer is closely related to its free volume, and both of these properties depend on multiple factors, such as temperature, stress magnitude, and strain level. To explore the fundamental viscoelastic behavior of EPDM using free volume as a proxy for viscoelasticity, this article investigates the influence of temperature, stress magnitude, and strain level, as well as their combined effect, on the free volume through molecular dynamics (MD) simulations. An EPDM cross-linked molecular model was built and verified by comparing the simulation values of glass transition temperature, mechanical properties, and gas diffusivity with the experimental results reported in the literature. Then, the dependence of EPDM's fractional free volume on temperature, strain, and their combined effect was investigated via MD simulations, on the basis of which the applicability of various superposition principles was also evaluated.

Compound heterozygous variants in MOGS inducing congenital disorders of glycosylation (CDG) IIb.

This study is to present two Chinese siblings who were diagnosed with congenital disorders of glycosylation (CDG) IIb because of mannosyl-oligosaccharide glucosidase (MOGS) deficiency. The siblings visited our hospital due to "pulmonary infection". Facial dysmorphism including long eyelashes, blepharophimosis, depressed nasal bridge, and high palate was noted. Head MRI of the elder sister showed increased signals on T1W1, bilateral frontal gyrus stenosis, and thin corpus callosum. Both cases presented progressive hepatomegaly and elevated hepatic enzymes. Low immunoglobulin was discovered in the siblings. Compound heterozygous variants of NM_006302:c.1239_1267dup,p.Asp414Leufs*17, c.544 G > A,p.Gly182Arg, and c.1698C > A,p.Asp566Glu in MOGS were identified. Structural modeling demonstrated that the mutations were pathogenic to MOGS. Our study enriched the genetic and phenotypic spectrum of MOGS-CDG, and for children with facial dysmorphism, postnatal dyspnea, seizures, motor developmental delay, hypotonia, and immunological or gastrointestinal dysfunction, this disease should be highly suspected.

Performance validation of an amplicon-based targeted next-generation sequencing assay and mutation profiling of 648 Chinese colorectal cancer patients.

Next-generation sequencing (NGS) has become a promising approach for tumor somatic mutation detection. However, stringent validation is required for its application on clinical specimens, especially for low-quality formalin-fixed paraffin-embedded (FFPE) tissues. Here, we validated the performance of an amplicon-based targeted NGS assay, OncoAim™ DNA panel, on both commercial reference FFPE samples and clinical FFPE samples of Chinese colorectal cancer (CRC) patients. Then we profiled the mutation spectrum of 648 Chinese CRC patients in a multicenter study to explore its clinical utility. This NGS assay achieved 100% test specificity and 95-100% test sensitivity for variants with mutant allele frequency (MAF) ≥ 5% when median read depth ≥ 500×. The orthogonal methods including amplification refractory mutation system (ARMS)-PCR and Sanger sequencing validated that NGS generated three false negatives (FNs) but no false positives (FPs) among 516 clinical samples for KRAS aberration detection. Genomic profiling of Chinese CRC patients with this assay revealed that 63.3% of the tumors harbored clinically actionable alterations. Besides the commonly mutated genes including TP53 (52.82%), KRAS (46.68%), APC (24.09%), PIK3CA (18.94%), SMAD4 (9.47%), BRAF (6.15%), FBXW7 (5.32%), and NRAS (4.15%), other less frequently mutated genes were also identified. Statistically significant association of specific mutated genes with certain clinicopathological features was detected, e.g., both BRAF and PIK3CA were more prevalent in right-side CRC (p < 0.001 and p = 0.002, respectively). We concluded this targeted NGS assay is qualified for clinical practice, and our findings could help the diagnosis and prognosis of Chinese CRC patients.

Whole-exome Sequencing Helps the Diagnosis and Treatment in Children with Neurodevelopmental Delay Accompanied Unexplained Dyspnea.

Neurodevelopmental delay accompanied unexplained dyspnea is a highly lethal disease in clinic. This study is to investigate the performance characteristics of trio whole exome sequencing (Trio-WES) in a pediatric setting by presenting our patient cohort and displaying the diagnostic yield. A total of 31 pediatric patients showing neurodevelopmental delay accompanied unexplained dyspnea were admitted to our hospital and referred for molecular genetic testing using Trio-WES. Eight genes namely MMACHC, G6PC, G6PT, ETFDH, OTC, NDUFAF5, SLC22A5, and MAGEL2 were suspected to be responsible for the onset of the clinical symptoms and 6 variants were novel. Standard interpretation according to ACMG guideline showed that the variants were pathogenic. Finally, diagnosis of methylmalonic aciduria and homocystinuria, glycogen storage disease, ornithine transcarbamylase deficiency, glutaric acidemia II, mitochondrial complex 1 deficiency, carnitine deficiency, and Schaaf-Yang syndrome was made in 12 out of the 31 patients. Trio-WES is an effective means for molecular diagnosis of infantile neurodevelopmental delay accompanied unexplained dyspnea. As for molecular etiology identification, when routine potential monogenetic inheritance patterns including de novo, autosomal recessive, autosomal dominant, and X-linked recessive inheritance analysis is negative, physicians should take into account imprinted genes.

De Novo Mutation of Paternal IGF2 Gene Causing Silver-Russell Syndrome in a Sporadic Patient.

Silver-Russell syndrome (SRS) is a rare, but well-recognized disease characterized by growth disorder. To date, there are two reports arguing IGF2 mutation for the onset of SRS. Herein, we present another sporadic case harboring IGF2 mutation. The male proband was the first and only child of a non-consanguineous Chinese couple. He was small for gestational age, with relative macrocephaly at birth. Severe feeding difficulties, low feeding, and growth retardation were revealed during neonatal period. At 4.5 years old, obvious body asymmetry was noted. Whole exome sequencing identified a novel de novo c.101G > A (p.Gly34Asp, NM_000612) variant in IGF2 and Sanger sequencing validated the variant. Amplification refractory mutation system polymerase chain reaction demonstrated that the IGF2 variant was on the paternal allele. Alignment shows the variant is evolutionarily conserved. Structural modeling argues that the variant site might be important for the binding of IGF2 to its receptor. Our study provides further evidence that IGF2 mutation may be another mechanism of SRS, and we consider that IGF2 should be included in a disease specific gene panel in case it is designed for SRS routine diagnostics.

Novel NFU1 Variants Induced MMDS Behaved as Special Leukodystrophy in Chinese Sufferers.

Multiple mitochondrial dysfunctions syndrome (MMDS) is an autosomal recessive disorder of systemic energy metabolism. This study is to present the diagnosis of two MMDS Chinese sufferers. Physical and auxiliary examination was performed. Next generation sequencing (NGS) was conducted to identify candidate causal genes and Sanger sequencing was adopted to validate the variants detected. Fluorescence quantitative polymerase chain reaction (FQ-PCR) amplification was carried out to testify allelic loss existence. Structural investigation was performed to study the possibility of the candidate variants for disease onset. Physical examination showed that the children were with neurological impairment. Auxiliary examination demonstrated energy metabolism disturbance and abnormal brain signals. NGS found that the probands had homozygous mutation of c.545 + 5G > A and compound heterozygous variants of exon 4 deletion and c.721G > T in NFU1, respectively. NFU1 was considered as candidate molecular etiology and indicating that the kids were with MMDS. Sanger sequencing confirmed the variants. FQ-PCR amplification characterized that patient 1 had a de novo allele mutation while patient 2 inherited from his parents. Structural investigation demonstrated that the variants were possible for MMDS occurrence. This is the first report of patients diagnosed as MMDS with novel mutation types from the Asia-Pacific region.