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At present, to settle the question of excessive noise in the speech signal during the call of mobile devices in China, the research proposes that the Wiener filter and the generative adversarial network are combined into the IGAN algorithm. Firstly, the Wiener filter regularization algorithm is introduced to construct the preprocessing model of the speech signal; then the preprocessing model is fused with the generative adversarial network algorithm to construct the denoising model. Finally, the performance analysis and simulation experiments of the application effect of the model are carried out. The results show that in the experiment comparing IGAN with five traditional algorithms, when the SNR ratio is increased to 17.5 dB, the MOS and PESQ scores under the IGAN method can reach 4.9 and 3.5 respectively, and the DNN effect is second only to IGAN. Other algorithms perform poorly. Then compare the number of iterations and the loss value between the two. When the network voice signal begins to converge, the loss value corresponding to DNN is 1.132; while the loss value of IGAN is about 0.573, it can be found that the loss value of IGAN has dropped by half, which shows that IGAN Build the model with a smaller loss value. And IGAN tends to converge when iteratively is performed for about 200 times, and the average peak SNR can reach up to 33.85 dB, an increase of nearly 1.02 dB, and the effect is remarkable. This all shows that the IGAN algorithm has the best denoising performance for network speech signals, improves the denoising efficiency, and is conducive to obtaining a denoising signal with a higher fit with the clean signal, so that mobile devices can better serve the people. [ABSTRACT FROM AUTHOR]

Introduction: Hutchinson-Gilford progeria syndrome is a rare pediatric genetic syndrome with an incidence of one per eight million live births. The disorder is characterized by premature aging, generally leading to death due to myocardial infarction or stroke at approximately 13.4 years of age. The genetic diagnosis and special clinical manifestation in two Han Chinese siblings observed at our clinic for genetic counseling are described in this report. We screened the LMNA gene in these two siblings as well as in their unaffected parents. A homozygous mutation R527C was identified in the affected siblings, and both parents were heterozygous for this variant.Case Presentation: In case 1, the elder 10-year-old female sibling showed the classic physical and radiological changes of Hutchinson-Gilford progeria syndrome in addition to a considerable overlap with the phenotype of mandibuloacral dysplasia.In case 2, the younger male sibling had begun to show some early physical changes at age six months.Conclusion: The phenotypic findings in the patients we describe here widen the clinical spectrum of Hutchinson-Gilford progeria syndrome symptoms, providing further recognition of the phenotypic range of LMNA-associated diseases. [ABSTRACT FROM AUTHOR]

Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10−4). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10−6). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10−3) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk. [ABSTRACT FROM AUTHOR]

Background: SHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide., Methods: In this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants., Results: Two novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM&#95;012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM&#95;012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions., Conclusion: We identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2 -related disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Li, Tan and Luo.)

Hemophilia A (HA), a common bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII), has long been considered an attractive target for gene therapy studies. However, full-length F8 cDNA cannot be packaged efficiently by adeno-associated virus (AAV) vectors. As the second most prevalent mutation causing severe HA, F8 intron 1 inversion (Inv1) is caused by an intrachromosomal recombination, leaving the majority of F8 (exons 2-26) untranscribed. In theory, the truncated gene could be rescued by integrating a promoter and the coding sequence of exon 1. To test this strategy in vivo , we generated an HA mouse model by deleting the promoter region and exon 1 of F8 . Donor DNA and CRISPR/SaCas9 were packaged into AAV vectors and injected into HA mice intravenously. After treatment, F8 expression was restored and activated partial thromboplastin time (aPTT) was shortened. We also compared two liver-specific promoters and two types of integrating donor vectors. When an active promoter was used, all of the treated mice survived the tail-clip challenge. This is the first report of an in vivo gene repair strategy with the potential to treat a recurrent mutation in HA patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luo, Li, Dai, Zhang, Liang, Li, Zeng, Su, Wang, Liang, Wu and Liang.)

Fabry disease (FD) was an X-linked lysosomal storage disorder resulting from a deficiency in glycosphingolipid catabolism caused by mutations in the α-galactosidase A gene GLA. Variant FD patients did not present with classical symptoms during childhood and were undiagnosed or misdiagnosed with other kidney diseases, such as chronic glomerulonephritis (CGN). In this study, we utilized exome sequencing and Sanger sequencing identified the variation p.E66Q of GLA completely co-segregated with the disease phenotype in a Chinese family, which previously been diagnosed as possible CGN. Female patients exhibited preferential X-chromosome inactivation (XCI) of the normal p.E66 allele, as indicated by XCI analysis. By measuring α-Gal A activity, we found that male patients in the pedigree had just little enzymatic activity while female patients had residual enzymatic activity. These patients were diagnosed with renal variant FD in subsequent clinical review. Our results directly implicated the GLA mutation p.E66Q as the genetic etiology of the Chinese renal variant FD pedigree., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Hutchinson-Gilford progeria syndrome is a rare pediatric genetic syndrome with an incidence of one per eight million live births. The disorder is characterized by premature aging, generally leading to death due to myocardial infarction or stroke at approximately 13.4 years of age. The genetic diagnosis and special clinical manifestation in two Han Chinese siblings observed at our clinic for genetic counseling are described in this report. We screened the LMNA gene in these two siblings as well as in their unaffected parents. A homozygous mutation R527C was identified in the affected siblings, and both parents were heterozygous for this variant., Case Presentation: In case 1, the elder 10-year-old female sibling showed the classic physical and radiological changes of Hutchinson-Gilford progeria syndrome in addition to a considerable overlap with the phenotype of mandibuloacral dysplasia.In case 2, the younger male sibling had begun to show some early physical changes at age six months., Conclusion: The phenotypic findings in the patients we describe here widen the clinical spectrum of Hutchinson-Gilford progeria syndrome symptoms, providing further recognition of the phenotypic range of LMNA-associated diseases.