Comprehensive bioinformatic analysis of Wnt1 and Wnt1-associated diseases.

Wnt1 is the first member of the Wnt family that was identified. It is phylogenetically conserved and essential for oncogenesis and multiple developmental processes. This study has summarized diseases and mutations related to Wnt1. Wnt1 is involved in various cancers, genetic type XV osteogenesis imperfecta, osteoporosis, and neurological diseases. The expression of Wnt1 in normal tissues and different types of cancers and the potential survival of cancer were analyzed using experiment-based bioinformatic analysis. Systematic analysis indicated that abnormal expression of Wnt1 is significantly associated with cancers, such as kidney renal carcinoma, hepatocellular carcinoma, thyroid carcinoma, head and neck squamous cell carcinoma, and uterine corpus endometrial carcinoma. GeneMANIA and STRING predicted that 32 proteins were involved with Wnt1 in Wnt signaling pathways and sorting and secretion of Wnts. These interacting molecules significantly co-occurred according to cBioPortal analysis. Thirty-three genes with an alteration frequency of more than 50% were observed in several cancers like esophageal squamous cell carcinoma, melanoma, and non-small cell lung cancer. Functional and experiment-based bioinformatics indicated that Wnt1 may act as a target of a potential biomarker for various types of human cancers. Wnt1 and other Wnt1-related proteins and signaling pathways may be ways to treat osteoporosis.

Health assessment of patients with achondroplasia, pseudoachondroplasia, and rickets based on 3D non-linear diagnostics.

The goal of this study was to analyze diminishment of the functional status of the skeleton, parts of organs, regions of the brain, connective tissues, and chondrocytes in patients with achondroplasia (ACH), pseudoachondroplasia (PSACH), and rickets. Three-dimensional non-linear scanning (3D-NLS) was used to analyze the functional status of patients with genetic bone disorders, including 7 patients with ACH, 3 patients with PSACH, and 3 patients with rickets. Results indicated that the percentage of patients with long bones in the decompensatory phase did not differ depending on whether they had ACH, PSACH, or rickets. Joints in the decompensatory phase did not differ in patients with ACH except for the right hip (16.67%). Various joints were in the decompensatory phase (16.7-33.3%) in patients with rickets. The thoracic vertebrae, lumbar vertebrae, and liver were in the decompensatory phase in all 3 groups of patients. Connective tissues were in the decompensatory phase in 33.33% of patients with ACH. None of the patients with PSACH had chondrocytes in the decompensatory phase but 66.67% of patients with ACH or rickets did. Regions of the brain in the decompensatory phase were most prevalent in patients with rickets or ACH but not in patients with PSACH. In conclusion, diagnosis based on 3D-NLS was able to identify the functional status of genetic bone disorders. Some areas of decompensation were common to the 3 diseases studied but other areas were specific to a given disease.

Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen.

Type I collagen is an important structural protein of bone, skin, tendon, ligament and other connective tissues. It is initially synthesized as a precursor form, procollagen, consisting of two identical pro-α1(I) and one proα2(I) chains, encoded by COL1A1 and COL1A2, respectively. The N- and C- terminal propeptides of procollagen are cleavage by N-proteinase and C-proteinase correspondingly, to form the central triple helix structure with Gly-X-Y repeat units. Mutations of COL1A1 and COL1A2 genes are associated with osteogenesis imperfecta, some types of Ehlers-Danlos syndrome, Caffey diseases, and osteogenesis imperfect/Ehlers- Danlos syndrome overlapping diseases. Clinical symptoms caused by different variations can be variable or similar, mild to lethal, and vice versa. We reviewed the relationship between clinical manifestations and type I collagen - related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders.

Splice receptor-site mutation c.697-2A>G of the COL1A1 gene in a Chinese family with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and blue sclerae, which are mainly caused by a mutation of the COL1A1 or COL1A2 genes that encode type I procollagen. Mutations in the splice site of type I collagen genes are one of the mutations that cause OI and usually lead to a mild or moderate OI phenotype. A heterozygous A to G point mutation in intron 9 at the -2 position of the splice receptor site of COL1A1 was identified in a family with type I or IV OI. Three affected individuals in four generations of one family all presented with several clinical symptoms. They all had pectus carinatum, flat feet, gray-blue sclerae, and normal stature, teeth, hearing, and vision. Forearm fractures, small joint dislocations, and muscle weakness were all present in the patient's father and grandmother, who presented with a moderate type IV phenotype. The 10-year-old proband with type I OI had suffered a fracture twice, but had no history of joint dislocation or skin hyperextensibility. Charting the family helped to identify clinical symptoms in patients with mutations at the N-terminal of type I collagen genes.