BACKGROUND: Colorectal cancer in children and adolescents is an exceptional condition. Its clinical symptoms are non-specific, leading to delayed diagnosis and poor prognosis.
METHODS: The present article reports the case of a 15-year-old child followed for acute lymphoblastic leukemia with a history of a grandfather operated on and followed for colorectal cancer. The child was admitted to our department with an occlusive syndrome. Endoscopy and radiological findings suggested the diagnosis of colon adenocarcinoma (AC). The therapeutic decision was a segmental colectomy covering the right colonic angle and colostomy followed by chemotherapy.
CONCLUSIONS: Colorectal cancer remains an exceptional pathology in children. They often include abdominal pain, nausea, vomiting and rectal discharge. Endoscopy is the key diagnostic test, enabling both distal and proximal lesions to be detected. Primary CA of the colon is rare in children, and even rarer as a second malignancy.
CONCLUSIONS: The clinical symptoms of colorectal adenocarcinoma in children are non-specific. These cancers are little-known in pediatrics, and are often diagnosed at an advanced stage.

OBJECTIVE: To systematically review the literature regarding the concordance of sleep bruxism (SB) between monozygotic (MZ) and dizygotic (DZ) twins.
METHODS: The registration for this systematic review was accomplished in the International Prospective Register of Systematic Reviews (PROSPERO, No. CRD42021251751). As of July 2022, four databases were searched, including PubMed, Scopus, Embase, and Web of Science, as well as the grey literature in Google Scholar and OpenGrey. Observational studies evaluating SB in MZ and DZ twins of any age and sex were included. For the evaluation of the risk of bias, the Joanna Briggs checklist was utilized. The certainty of evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Pooled and subgroup meta-analyses were performed to estimate concordance of SB ​​between twins (p < 0.05).
RESULTS: In total, 3,155 records were identified. In the qualitative analysis, eleven studies were included; of these, seven were included in the meta-analysis. The majority of the articles exhibited a low risk of bias (63.6%). Greater SB concordance was observed between MZ twins than between DZ twins in the analysis of general concordance (OR = 1.47; 95% CI = 1.07-2.02) and also positive concordance (OR = 1.53; 95% CI = 1.29-1.81). Within the subgroup analyses, the significance of the findings remained only for the reported/self-reported SB regarding general concordance (OR = 1.44; 95% CI = 1.07-1.95) and positive concordance (OR = 1.55; 95% CI = 1.28-1.88). Low certainty of the evidence was observed for the general concordance analysis, while moderate certainty was observed for the positive concordance.
CONCLUSIONS: There was a higher concordance of SB in MZ twins compared to DZ twins, indicating a possible genetic influence on the condition\'s occurrence.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease of the brain characterized by progressive white matter lesions, subcortical infarcts, and cognitive decline. This autosomal dominant disorder is caused by mutations in the NOTCH3 gene located on chromosome 19, resulting in the accumulation of granular osmiophilic material within the walls of small arteries and arterioles. Clinically, CADASIL typically manifests in mid-adulthood with recurrent ischemic events, migraine with aura, mood disturbances, and cognitive impairment. Neuroimaging plays a crucial role in the diagnosis of CADASIL, with characteristic findings including white matter hyperintensities particularly in the anterior temporal lobe and external capsule.

Genetic testing in patients with ovarian carcinoma (OC) is crucial, as around 10-15% of these women have a genetic predisposition to OC. Although guidelines have recommended universal germline testing for all patients with OC for a decade, implementation has proved challenging, thus resulting in low germline-testing rates (around 30-50%). Many new initiatives to improve genetic-testing rates have emerged, but most have been carried out at the local level, leading to differences in workflows within and between countries. We present an example of a nationwide implementation project that has successfully led to a uniform, high-quality genetic-testing workflow for women with OC. Nationwide multidisciplinary meetings generated consensus on the preferred workflow for OC genetic testing: the \"Tumor-First\" workflow. This workflow means starting by testing the tumor DNA for the presence of pathogenic variants in OC-risk genes, thus providing a prescreen to germline testing while yielding information on the effectiveness of treatment with PARP inhibitors. This new workflow efficiently stratifies genetic counseling and germline testing and reduces healthcare costs. Although challenging, the nationwide implementation of this workflow was successful, resulting in tumor-DNA testing rates exceeding 80%. In this article, we present our structured implementation approach, illustrate our implementation strategies-which were tailored to identified factors important to implementation-and share the lessons learned from the Tumor-First implementation project. This knowledge could facilitate the future implementation of workflows aimed at optimizing the recognition of hereditary cancers.

Gregor Mendel developed the principles of segregation and independent assortment in the mid-1800s based on his detailed analysis of several traits in pea plants. Those principles, now called Mendel\'s laws, in fact, explain the behavior of genes and alleles during meiosis and are now understood to underlie \"Mendelian inheritance\" of a wide range of traits and diseases across organisms. When asked to give examples of inheritance that do NOT follow Mendel\'s laws, in other words, examples of non-Mendelian inheritance, students sometimes list incomplete dominance, codominance, multiple alleles, sex-linked traits, and multigene traits and cite as their sources the Khan Academy, Wikipedia, and other online sites. Against this background, the goals of this Perspective are to (1) explain to students, healthcare workers, and other stakeholders why the examples above, in fact, display Mendelian inheritance, as they obey Mendel\'s laws of segregation and independent assortment, even though they do not produce classic Mendelian phenotypic ratios and (2) urge individuals with an intimate knowledge of genetic principles to monitor the accuracy of learning resources and work with us and those resources to correct information that is misleading.

Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.

Heritable gene silencing has been proposed to rely on DNA methylation, histone modifications, and/or non-coding RNAs in different organisms. Here we demonstrate that multiple RNA-mediated mechanisms with distinct and easily detectable molecular signatures can underlie heritable silencing of the same open-reading frame in the nematode C. elegans. Using two-gene operons, we reveal three cases of gene-selective silencing that provide support for the transmission of heritable epigenetic changes through different mechanisms of RNA silencing independent of changes in chromatin that would affect all genes of an operon equally. Different heritable epigenetic states of a gene were associated with distinct populations of stabilized mRNA fragments with untemplated poly-UG (pUG) tails, which are known intermediates of RNA silencing. These \'pUG signatures\' provide a way to distinguish the multiple mechanisms that can drive heritable RNA silencing of a single gene.

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.
目的： 分析遗传性高非结合性胆红素血症患者尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）突变基因（包括增强子、启动子、外显子1～5）分布特征，探讨UGT1A1基因型与临床表型的关系。 方法： 回顾性分析2015年6月至2022年12月在南京市第二医院诊断为遗传性高非结合性胆红素血症的患者资料。患者均采用Sanger测序对UGT1A1基因进行检测，完成血常规、肝生物化学、腹部影像学检查。分类变量资料比较采用χ (2)检验或fisher精准检验；正态分布连续变量资料比较用t检验。 结果： 112例（男∶女为81∶31，年龄9～70岁）遗传性高非结合性胆红素血症患者，共查出14个突变位点，7个为已证实的突变，频率由高到低；(TA)n占50%、c.211G > A(p.G71R）占49.10%、1456T > G(p.Y486D）占16.96%、c.686C > A(p.R229W）占12.5%、1091C > T(p.P364L）占8.04%、c.-3279T > G占0.982%。所有患者同时存在1～4个突变，其中只有1个突变病例最多见（55.36%），其次为2个突变（37.5%），3和4个突变较为少见（分别为5.36%，1.78%）；4组间总胆红素（TBil）水平差异无统计学意义(F = 0.652，P = 0.583）。一个突变以(TA)n和c.211G > A(p.G71R）最多见，其中TA6/TA7 (n = 10）与TA7/TA7 (n = 14）突变患者TBil差异有统计学意义(t = 2.143，P = 0.043）。c.211G > A(p.G71R）杂合（n = 9）与纯合（n = 15）突变的TBil差异无统计学意义（t  = 0.382，P = 0.706）。GS组占75%，中间组占16.9%，CNS-Ⅱ组占8%，3组TBil差异有统计学意义（F = 270.992，P < 0.001）；GS组、中间组、CNS-Ⅱ组中1个突变（分别为44、14、4例）与≥2个突变（分别为40、5、5例）差异无统计学意义（χ (2) = 3.317，P = 0.19）。 结论： 遗传性高非结合性胆红素血症患者UGT1A1基因变异位点数量对TBil水平可能无叠加作用。TA7/TA7突变并不少见，TBil水平较高。.

Interacting molecules create regulatory architectures that can persist despite turnover of molecules. Although epigenetic changes occur within the context of such architectures, there is limited understanding of how they can influence the heritability of changes. Here, I develop criteria for the heritability of regulatory architectures and use quantitative simulations of interacting regulators parsed as entities, their sensors, and the sensed properties to analyze how architectures influence heritable epigenetic changes. Information contained in regulatory architectures grows rapidly with the number of interacting molecules and its transmission requires positive feedback loops. While these architectures can recover after many epigenetic perturbations, some resulting changes can become permanently heritable. Architectures that are otherwise unstable can become heritable through periodic interactions with external regulators, which suggests that mortal somatic lineages with cells that reproducibly interact with the immortal germ lineage could make a wider variety of architectures heritable. Differential inhibition of the positive feedback loops that transmit regulatory architectures across generations can explain the gene-specific differences in heritable RNA silencing observed in the nematode Caenorhabditis elegans. More broadly, these results provide a foundation for analyzing the inheritance of epigenetic changes within the context of the regulatory architectures implemented using diverse molecules in different living systems.

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