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Background: Mutations in CD40 ligand gene (CD40L) affecting immunoglobulin class-switch recombination and somatic hypermutation can result in X-Linked Hyper IgM Syndrome (HIGM1, XHIGM), a kind of rare serious primary immunodeficiency disease (PID) characterized by the deficiency of IgG, IgA and IgE and normal or increased serum concentrations of IgM. The objective of this study is to explain genotype-phenotype correlation and highlight the mutation responsible for a Chinese male patient with XHIGM. Methods: Whole exome sequencing (WES) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutation in the XHIGM family. Results: The results of the sequencing revealed that a new causative mutation in CD40L (c.714delT in exon 5, p.F238Lfs*4) which leads to the change in amino acids (translation terminates at the third position after the frameshift mutation) appeared in the proband. As his mother in the family was carrier with this heterozygous mutation, the hemizygous mutation in this patient came from his mother indicating that genetic mode of XHIGM is X-linked recessive inheritance. Conclusion: This study broadens our knowledge of the mutation in CD40L and lays a solid foundation for prenatal diagnosis and genetic counseling for the XHIGM family. [ABSTRACT FROM AUTHOR]

Smith-Fineman-Myers syndrome (SFMS) is a rare inherited disorder characterized mainly by mental retardation and anomalies in the appearance of patients. SFMS is caused by a mutation in the α-thalassemia/mental retardation syndrome X-linked (ATRX) gene and has an X-linked recessive pattern. In the present study, a novel ATRX mutation was identified, and the association between its genotype and the phenotype was explored in a Chinese Han family with SFMS. This study aimed to lay a foundation for prenatal diagnosis for this family. Briefly, genomic DNA was extracted from peripheral blood samples obtained from the family. High-throughput genetic sequencing was employed to detect the whole exome; subsequently, Sanger sequencing was performed to verify the candidate mutations. Clinical analysis of the proband was also accomplished. Consequently, a novel missense ATRX mutation was identified comprising a single nucleotide change of C to T, which caused an amino acid substitution at codon 172 in exon 7 (c.515C>T; p.Thr172Ile) of the proband. This mutation was found to co-segregate in the present SFMS pedigree and was located in a highly conserved region of the ATRX protein, thus suggesting that it may be a pathogenic mutation. Taken together, these findings provided novel information that may lead towards an improved understanding of the genetic and clinical features of patients with SFMS, thereby facilitating a more accurate prenatal diagnosis of SFMS. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods: Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results: Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion: Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI. [ABSTRACT FROM AUTHOR]

Background and Aims: 125 I radioactive particles implantation have demonstrated efficacy in eradicating hepatocellular carcinoma (HCC). However, progressive resistance of HCC to 125 I radioactive particles has limited its wide clinical application., Methods: We investigated the cellular responses to 125 I radioactive particles treatment and autophagy-related 9B (ATG9B) silencing in HCC cell lines and Hep3B xenografted tumor model using Cell Counting Kit-8 reagent, western blotting, immunofluorescence, flow cytometry, transmission electron microscopy and immunohistochemistry., Results: In this study, we demonstrated that 125 I radioactive particles induced cell apoptosis and protective autophagy of HCC in vitro and in vivo . Inhibition of autophagy enhanced the radiosensitivity of HCC to 125 I radioactive particles. Moreover, 125 I radioactive particles induced autophagy by upregulating ATG9B, with increased expression level of LC3B and decreased expression level of p62. Furthermore, ATG9B silencing downregulated LC3B expression and upregulated p62 expression and enhanced radiosensitivity of HCC to 125 I radioactive particles in vitro and in vivo ., Conclusions: Inhibition of ATG9B enhanced the antitumor effects of 125 I particle radiation against HCC in vitro and in vivo. Our findings suggest that 125 I particle radiation plus chloroquine or/and the ATG9B inhibitor may be a novel therapeutic strategy for HCC., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Background: The preferred therapy for patients with pulmonary nodules which highly suspected as lung cancer by low-dose spiral computed tomography (CT) is surgery, but the best screening method of whole body is not clear yet. The aim of this study is to investigate the differences in the progression-free survival (PFS) of patients with Ia stage non-small cell lung cancer after screening of positron emission computed tomography (PET)-CT and conventional imaging (B-ultrasound/CT/MRI/ECT, BCME)., Methods: A total of 300 cases of Ia stage non-small cell lung cancer were collected, of which 170 cases were performed PET-CT and 130 cases were performed BCME before operation. The basic characteristics of the two groups were analyzed by propensity score matching (PSM), and 114 cases of each group were included in the study. The survival analysis was carried out by the Kaplan-Meier survival curve and the Cox regression analysis., Results: There was no significant difference between each group analyzed by PSM. The PFS of PET-CT and BCME were (44.9±27.2) months and (44.1±33.1) months (χ2=1.284, P=0.257). Both of the method ssucceed in screening. It is not the PFS influence factors. The false positive of PET-CT and BCME were 10 cases and 8 cases (χ2=0.241, P=0.623)., Conclusions: Both PET-CT and BCME can be used as a screening method for Ia stage non-small cell lung cancer according to individualized choice of patients.