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Proteus syndrome is a rare congenital hamartomatous syndrome characterized by the asymmetric and disproportionate overgrowth of limbs, emergence of connective tissue nevi, epidermal nevi, ysregulated adipose tissue, and vascular malformations. The Proteus syndrome is caused by mosaicism of somatic activating mutation in the AKT1 gene which locates at chromosome 14q32.3. This syndrome is extremely rare, making it difficult to diagnose. The most commonly used diagnostic criteria are too complicated to be used in clinical practice. Surgery can partially alleviate the clinical symptoms of overgrowth, but it can't inhibit the progression of the disease. This article summarizes the diagnostic criteria, treatment principles, and perioperative managements for Proteus syndrome in the world. The article proposes the highly suspected morphological manifestations of Proteus syndrome was based on clinical experiences of the author.The article emphasizes using genetic detection of pathological tissue as the gold standard for diagnosis, and suggests targeted therapy as the optimal treatment for Proteus syndrome.
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Objective:To explore the value of single nucleotide polymorphism for molecular warning of hypertensive intracerebral hemorrhage in Li Nationality in Hainan.Methods:Totally 56 patients with hypertensive intracerebral hemorrhage of Li Nationality in Hainan Province, 100 healthy controls of Li nationality and 203 healthy controls of Han nationality in Hainan Province from January 2019 to October 2020 were selected as the research subjects.After genomic DNA was extracted, rs2494739, rs2494744 and rs2498794 of AKT1 gene were genotyped and analyzed by SPSS 25.0 to explore the differences between Han and Li Nationality, and between Li healthy population and intracerebral hemorrhage population.Results:There was no difference in the frequencies of rs2498794, rs2494739 and rs2494744 polymorphisms of AKT1 gene among Han and Li healthy controls ( P>0.05). The rates of AA, AG and GG at rs2498794 locus in Li Nationality patients with intracerebral hemorrhage (14.28%, 39.29% and 46.43%) were significantly different from those of Li control group (44.00%, 47.00% and 9.00%)( P<0.05). The distribution rates of AA, AG and GG of rs2494744 in Li Nationlity patients with intracerebral hemorrhage were 57.14%, 37.50% and 5.36%, respectively, which were statistically significant compared with the control group (20.00%, 44.00% and 36.00%) ( P<0.05). The incidence of CC, CT and TT at rs2494739 locus in Hainan Li Nationality patients were 14.28%, 46.43% and 39.29% respectively, which were also significantly different from those in Li control group(34.00%, 41.00% and 25.00%) ( P<0.05). The incidence of rs2494744-A in intracerebral hemorrhage group (75.89%) was much higher than that in Li control group (42.00%), and the OR value of rs2494744-A was 4.35.The incidence of rs2498794-G in intracerebral hemorrhage group and control group were 66.07% and 32.50%, respectively, and the OR was 4.04.Alleles rs2494744-A and rs2498794-G were moderately associated with the incidence of intracerebral hemorrhage ( P<0.05). Conclusion:rs2494744-AA, rs2498794-GG and alleles rs2494744-A and rs2498794-G are the risk factors of HICH in Li nationality, which is of great value to the construction of its molecular early warning system.
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Objective:To investigate the early warning effect of two polymorphisms of AKT1 gene (rs1130214, rs2494744) on the risk of atherosclerotic cerebral infarction in Hainan province.Methods:In this study, totally 243 patients with atherosclerotic cerebral infarction who were hospitalized of Hainan Province from January 2019 to October 2020 were selected as the cerebral infarction group, including 148 Han nationality people and 95 Li nationality people. And 272 healthy people who received physical examination in the same hospital during the same period were selected as the control group, including 197 Han nationality people and 75 Li nationality people.All participants signed informed consent. The peripheral anticoagulant DNA was collected, and the genomic DNA was extracted and amplified by PCR.The genotypes of rs1130214 and rs2494744 were analyzed by mass spectrometry, and the distribution frequency of genotypes in cerebral infarction group and control group was analyzed by Chi-square test with SPSS 25.0 software.Results:Regardless of nationality, there was no significant difference in the distribution frequency of rs1130214 and rs2494744 of AKT1 gene between cerebral infarction group and control group (both P>0.05). The frequencies of AA, AG and GG genotypes of rs2494744 locus were 44.59%, 51.36% and 4.05% in the cerebral infarction group of Han nationality, while they were 47.21%, 42.13% and 10.66% in the control group of Han nationality, with significant difference between the two groups(χ 2=6.396, P<0.05). The independent effects of the three genotypes were analyzed by regression analysis. The results showed that GG genotype might be a resistance factor of cerebral infarction in Han population ( P=0.024, OR=0.354, 95% CI: 0.139-0.901). The frequency of AA, AG and GG genotypes of rs2494744 was 58 (61.05%), 25 (26.32%), 12 (12.63%) in the control group of Li nationality, and 28 (37.33%), 39 (52.00%), 8 (10.67%) in the control group of Li nationality. The results showed that the distribution of AA was significantly higher than that of the control group ( P<0.05, OR= 2.631, 95% CI=1.410-4.09), while AG was on the contrary ( P<0.05, OR=0.330, 95% CI=0.173-0.627). Conclusion:AA genotype of rs2494744 in AKT1 gene polymorphism is a risk factor for cerebral infarction in Li nationality group, which has potential early warning value for cerebral infarction in Hainan Li nationality group, while AG has protective effect on cerebrovascular health in Hainan Li nationality group.
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Objective To investigate the expression of miR-34a-5p and AKT1 genes in endometrium tissues of patients with endometriosis (EM) and their effects on migration and invasion of endometrial stromal cells (ESCs). Methods A total of 91 patients, undergone hysterectomy in the Department of Obstetrics and Gynecology of Zhujiang Hospital of Southern Medical University from Jan. 2018 to Jun. 2019 due to benign gynecological diseases, were collected and divided into EM group (68 cases) and non-EM group (23 cases). The expressions of miR-34a-5p and AKT1 genes in endometrium tissues of patients were detected by in situ hybridization and immunohistochemistry. ESCs were transfected with miR-34a-5p mimic and negative control RNA (miR-NC) using liposome-3000 to construct the cell models of miR-34a-5p mimic group and miR-NC group. The cell proliferation rate was detected by CCK-8 method, and cell migration, invasion, apoptosis and autophagy ability experiments were performed to determine the effect of miR-34a-5p on ESCs' proliferation, migration, invasion, apoptosis and autophagy. Results The positive expression rate of miR-34a-5p was lower, and of AKT1 was higher in EM group than those in non-EM group (16.2% vs. 82.6%, X2=34.323; 72.1% vs. 30.4%, X2=12.581, P<0.001). After culturing for 12, 24 and 48 h, the cell proliferation rate was higher in miR-NC group than that in miR-34a-5p mimic group (P<0.05). The cell migration ability and invasion ability were higher in miR-NC group than those in miR-34a-5p mimic group with statistically significant difference [(65.00%±5.00%) vs. (30.67%±4.04%); (88.0±8.5) vs. (32.3±6.1), t=9.179, P<0.05]. The cell apoptosis rate and the expression level of LC3 gene were obviously lower in miR-NC group than those in miR-34a-5p mimic group [(9.33%±3.51%) vs. (18.00%±2.00%); (0.19±0.04) vs. (0.39±0.03), t=8.02, P<0.05]. Conclusion miR-34a-5p may be involved in the pathogenesis of EM by targeting AKT1 genes to affect the proliferation, migration, invasion, apoptosis and autophagy function of ESC.
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Objective Proteus syndrome is a rare disease. The aim of the present study was to analyze the clinical characteristics and gene mutations of Proteus syndrome with a case report and relevant literature review. Methods Clinical data of the patient with Proteus syndrome were collected in detail and biochemical measurements and radiological examinations were conducted. Tissues from phalanges with lesions were obtained to extract DNA, and Sanger sequencing of AKT1 gene was carried on. The pathogenic mutation was further tested in peripheral blood samples of the patient, his parents and 250 healthy volunteers. Orthopaedic surgery was performed on the affected limbs of the patient. Results The patient was presented with progressive overgrowth of the right extremity, scoliosis, cerebral connective tissue nevus and lower extremity venous. A heterozygous mutation of AKT1 gene (c. 49G>A) was identified in DNA extracted from the affected bone tissue of the patient, but not be found in genomic DNA of peripheral blood samples from the patient, his parents and 250 healthy volunteers. Movement function of the affected limb improved significantly after the operations. Conclusions The prominent features of Proteus syndrome are overgrowth of one extremity and cerebral connective tissue nevus. A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease.
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OBJECTIVE: We performed a genetic association study with schizophrenic patients to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1) gene plays a role in obstetric complications. METHODS: One-hundred-eighty patients with schizophrenia (male, 113; female, 67) were included. All patients fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were measured by the Lewis scale. Prenatal and perinatal information was retrospectively collected from the patients' mothers. We selected six single nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA (rs2498804). The genotype data were analyzed for an association with the Lewis total score in terms of allele, genotype, and haplotype distribution. RESULTS: The mean total Lewis scores were 1.30+/-1.61 for males and 1.54+/-1.87 for females. Higher total score tended to be correlated with an earlier age of onset of schizophrenia in females. In the total sample, no SNP was associated with obstetric complications. However, the additional analyses for male and female subgroups found a significant association between SNPA and SNP4 and Lewis score in females (p=0.02 for SNPA, p=0.04 for SNP4). The SNP5-SNPA haplotype showed a positive association with obstetric complications (p=0.03) in the female patient group. CONCLUSION: We found an association between SNPs in the AKT1 gene and total Lewis score measuring obstetric complications in female patients with schizophrenia. Because these findings did not survive a correction for multiple testing, the significance should be interpreted carefully and replication studies are required.