A novel APC mutation associated with Gardner syndrome in a Chinese family.

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

Biological research on the occurrence and development of multiple myeloma and its treatment.

INTRODUCTION: To review the pathogenesis and treatment of multiple myeloma (MM). MM is a hematological malignancy with abnormal plasma cell proliferation in bone marrow. Due to the emergence of drug resistance, MM is still an incurable malignancy, which requires further exploration of pathogenesis and effective therapeutic targets. METHODS: In this paper, the method of literature review is adopted to obtain the information about MM. Based on the literature, comprehensive and systematic review is made. RESULTS: MM is a complex pathophysiological process with great heterogeneity, mainly reflected in genomic instability and bone marrow microenvironment. At present, the treatment of MM has made great progress, proteasome inhibitors and immunomodulatory drugs are widely used in clinic. Allogeneic stem cell transplantation may be the only promising cure for MM, and its high transplant-related mortality limits its clinical application. CONCLUSIONS: The future of MM treatment lies in the development of more targeted therapies, novel immunotherapies, and a better understanding of the disease's molecular and genetic basis.

Identification of a novel missense heterozygous mutation in the KDF1 gene for non-syndromic congenital anodontia.

OBJECTIVES: KDF1 is a recently identified gene related to tooth development, but it has been little studied. To date, only three cases have been reported in which KDF1 mutations are related to tooth development, including two ectodermal dysplasia cases accompanied by tooth loss and one non-syndromic case with tooth agenesis. However, no KDF1 mutations have been reported as associated with non-syndromic anodontia. Here, the aim was to investigate the genetic etiology of this condition and explore the functional role of a novel KDF1 mutation in a Chinese patient with non-syndromic anodontia. MATERIALS AND METHODS: Pathogenic variants were identified by whole-exome and Sanger sequencing. Meanwhile, we conducted a literature review of the reported KDF1 mutations and performed an in vitro functional analysis of four anodontia-causing KDF1 mutations (one novel and three known). RESULTS: We identified a novel de novo missense mutation (c.911 T > A, p.I304N) in the KDF1 gene in a Chinese patient with severe non-syndromic anodontia. In vitro functional studies showed altered mRNA and protein expression levels of the mutant KDF1. CONCLUSIONS: Our results are the first report of KDF1 missense mutation causing non-syndromic anodontia. CLINICAL RELEVANCE: This study not only further supports the important role of KDF1 in non-syndromic congenital anodontia, but also expands the spectrum of KDF1 mutations and will contribute to the genetic diagnosis and counselling of families with anodontia.

Functional Analysis of Ectodysplasin-A Mutations in X-Linked Nonsyndromic Hypodontia and Possible Involvement of X-Chromosome Inactivation.

BACKGROUND: Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndrome hypohidrotic ectodermal dysplasia or nonsyndromic tooth agenesis. The influence of EDA mutations on dentinogenesis and odontoblast differentiation has not been reported. The aim of this study was to identify genetic clues for the causes of familial nonsyndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X-chromosome inactivation (XCI) in the blood of female carriers. RESULTS: In this study, we identified an EDA mutation in a Chinese family: the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele. CONCLUSIONS: In summary, we demonstrated that EDA mutations result in nonsyndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs. Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.