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Background: Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic OCA in a Chinese Han family.

Methods: We performed a comprehensive clinical examination of family members, screened for mutation loci using whole exome sequencing (WES) technology, and predicted mutations using In silico tools.

Results: The patient's clinical manifestations were white skin, yellow hair, a few freckles on the cheeks and bridge of the nose, decreased vision, blue iris, poorly defined optic disk borders, pigmentation of the fundus being insufficient, and significant vascular exposure. The WES test results indicate that the patient has compound heterozygous mutations in the OCA2 gene (c.1258G > A (p.G420R), c.1441G > A (p.A481T), and c.2267-2 A > C), respectively, originating from her parents. Among them, c.1258G > A (p.G420R) is a de novo mutation with pathogenic. Our analysis suggests that compound heterozygous mutations in the OCA2 gene are the primary cause of the disease in this patient.

Conclusions: The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G > A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.

Correction: Hereditas 156, 20 (2019).

https://doi.org/10.1186/s41065-019-0096-6.

Following publication of the original article [1], the author reported that Fig. 6B and 6C were repeated. The correct Figure is included here and the original article has been updated.

Diagnostic value of the five hub genes in identifying normal and breast cancer tissues. The ROC curve revealed that the mRNA levels of these five genes exhibited excellent diagnostic efficiency for breast cancer and adjacent tissues. (a) TPX2, (b) KIF2C, (c) CDCA8, (d) BUB1B, (E) CCNA2

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1. Cai Y, Mei J, Xiao Z, et al. Identification of five hub genes as monitoring biomarkers for Breast cancer Metastasis in silico. Hereditas. 2019;156:20. https://doi.org/10.1186/s41065-019-0096-6.

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1. Yun Cai, Jie Mei and Zhuang Xiao contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

1. Department of Physiology, Nanjing Medical University, Nanjing, 211166, China

   Yun Cai, Jie Mei, Zhuang Xiao, Bujie Xu, Xiaozheng Jiang & Yichao Zhu

2. Department of Bioinformatics, Nanjing Medical University, Nanjing, 211166, China

   Yun Cai

3. Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, China

   Yongjie Zhang

4. Key Laboratory for Aging & Diseases of Nanjing Medical University, Nanjing Medical University, Nanjing, 211166, China

   Yongjie Zhang

5. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China

   Yichao Zhu

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Background: Fibrinogen plays pivotal roles in multiple biological processes. Genetic mutation of the fibrinogen coding genes can result in congenital fibrinogen disorders (CFDs). We identified a novel heterozygous missense mutation, FGG c.1168G > T (NCBI NM_000509.6), and conducted expression studies and functional analyses to explore the influence on fibrinogen synthesis, secretion, and polymerization.

Methods: Coagulation tests were performed on the patients to detect the fibrinogen concentration. Whole-exome sequencing (WES) and Sanger sequencing were employed to detect the novel mutation. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cell lines were built to examine the recombinant fibrinogen synthesis and secretion by western blotting and enzyme-linked immunosorbent assay (ELISA). The functional analysis of fibrinogen was performed by thrombin-catalyzed fibrin polymerization assay. In silico molecular analyses were carried out to elucidate the potential molecular mechanisms.

Results: The clinical manifestations, medical history, and laboratory tests indicated the diagnosis of hypodysfibrinogenemia with bleeding phenotype in two patients. The WES and Sanger sequencing revealed that they shared the same heterozygous missense mutation, FGG c.1168G > T. In the expression studies and functional analysis, the missense mutation impaired the recombinant fibrinogen's synthesis, secretion, and polymerization. Furthermore, the in silico analyses indicated novel mutation led to the hydrogen bond substitution.

Conclusion: The study highlighted that the novel heterozygous missense mutation, FGG c.1168G > T, would change the protein secondary structure, impair the "A: a" interaction, and consequently deteriorate the fibrinogen synthesis, secretion, and polymerization.