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Ophthalmic Surgery, Lasers & Imaging... Jan 2024
Topics: Humans; Fluorescein Angiography; Retinal Perforations; Uveomeningoencephalitic Syndrome; Treatment Outcome
PubMed: 38189795
DOI: 10.3928/23258160-20231215-01 -
The Journal of Molecular Diagnostics :... Mar 2024Prenatal molecular genetic testing for familial variants that cause inherited disorders has been performed for decades and is accepted as standard of care. However, the...
Prenatal molecular genetic testing for familial variants that cause inherited disorders has been performed for decades and is accepted as standard of care. However, the spectrum of genes considered for prenatal testing is expanding because of genetic testing for hereditary cancer risk (HCR) and inclusion of conditions with associated cancer risk in carrier screening panels. A few of these disorders, such as ataxia telangiectasia and Bloom syndrome, include increased cancer risk as part of the phenotype, already meet professional guidelines for prenatal testing, and may be associated with increased cancer risk in heterozygous carriers. In addition, recent studies implicate heterozygosity for variants in lysosomal storage disease genes in HCR etiology. Currently, there is no specific professional guidance regarding prenatal testing for HCR. To determine the prevalence of such testing, we reviewed 1345 consecutive prenatal specimens received in our laboratory for familial variant-specific testing and identified 65 (4.8%) with a known or likely HCR component, plus 210 (15.6%) for lysosomal storage disease. These specimens were classified into five distinct categories for clarity and to enable evaluation. Our experience assessing prenatal specimens for variants associated with HCR, with or without a constitutional phenotype, provides metrics for and contributes to the points to consider in prenatal testing for HCR.
Topics: Female; Humans; Pregnancy; Genetic Predisposition to Disease; Genetic Testing; Lysosomal Storage Diseases; Neoplasms; Phenotype
PubMed: 38171482
DOI: 10.1016/j.jmoldx.2023.12.002 -
Rheumatology and Immunology Research Dec 2023The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut...
The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut microbiome and several autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) spondyloarthropathies (SpA), Sjogren's syndrome (SS), and systemic sclerosis (SSc). Evidence from studies of RA and SLE patients suggests that alterations in the gut microbiome composition and function contribute to disease development and progression through increased gut permeability, with microbes and microbial metabolites driving an excessive systemic activation of the immune system. Also, there is growing evidence that gut dysbiosis and subsequent immune cell activation may contribute to disease pathogenesis in SpA and SS. For SSc, there are fewer, but these are still informative, reports on alterations in the gut microbiome. In general, the complex interplay between the microbiome and the immune system is still not fully understood. Here we discuss the current knowledge of the link between the gut microbiome and autoimmune rheumatic diseases, highlighting potentially fertile areas for future research and make considerations on the potential benefits of strategies that restore gut microbiome homeostasis.
PubMed: 38125641
DOI: 10.2478/rir-2023-0027 -
Cell Death Discovery Nov 2023Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a...
Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.
PubMed: 38007566
DOI: 10.1038/s41420-023-01726-1 -
Orphanet Journal of Rare Diseases Nov 2023Poorly coordinated care can have major impacts on patients and families affected by rare conditions, with negative physical health, psychosocial and financial...
BACKGROUND
Poorly coordinated care can have major impacts on patients and families affected by rare conditions, with negative physical health, psychosocial and financial consequences. This study aimed to understand how care is coordinated for rare diseases in the United Kingdom.
METHODS
We undertook a national survey in the UK involving 760 adults affected by rare diseases, 446 parents/carers of people affected by rare diseases, and 251 healthcare professionals who care for people affected by rare diseases.
RESULTS
Findings suggested that a wide range of patients, parents and carers do not have coordinated care. For example, few participants reported having a care coordinator (12% patients, 14% parents/carers), attending a specialist centre (32% patients, 33% parents/carers) or having a care plan (10% patients, 44% parents/carers). A very small number of patients (2%) and parents/carers (5%) had access to all three-a care coordinator, specialist centre and care plan. Fifty four percent of patients and 33% of parents/carers reported access to none of these. On the other hand, a higher proportion of healthcare professionals reported that families with rare conditions had access to care coordinators (35%), specialist centres (60%) and care plans (40%).
CONCLUSIONS
Care for families with rare conditions is generally not well coordinated in the UK, with findings indicating limited access to care coordinators, specialist centres and care plans. Better understanding of these issues can inform how care coordination might be improved and embrace the needs and preferences of patients and families affected by rare conditions.
Topics: Adult; Humans; Caregivers; Cross-Sectional Studies; Rare Diseases; United Kingdom; Delivery of Health Care
PubMed: 37996938
DOI: 10.1186/s13023-023-02934-9 -
Biomedicine & Pharmacotherapy =... Dec 2023The high expression of BLM (Bloom syndrome) DNA helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor...
The high expression of BLM (Bloom syndrome) DNA helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to study the antitumor effect of fangchinoline derivative HY-2 by targeting BLM DNA helicase, and then explore its inhibitory mechanism on proliferation of MDA-MB-435 breast cancer cells. We confirmed that the mRNA and protein levels of BLM DNA helicase in breast cancer were higher than those in normal tissues. HY-2 could inhibit the DNA binding, ATPase and DNA unwinding of BLM DNA helicase with enzymatic assay. HY-2 could also inhibit the DNA unwinding of DNA helicase in cells. In addition, HY-2 showed an inhibiting the MDA-MB-435, MDA-MB-231, MDA-MB-436 breast cancer cells expansion. The mRNA and protein levels of BLM DNA helicase in MDA-MB-435 cells increased after HY-2 treatment, which might contribute to HY-2 inhibiting the DNA binding, ATPase and DNA unwinding of BLM DNA helicase. The mechanism of HY-2 inhibition on BLM DNA helicase was further confirmed with the effect of HY-2 on the ultraviolet spectrogram of BLM DNA helicase and Molecular dynamics simulation of the interacting between HY-2 and BLM DNA helicase. Our study provided some valuable clues for the exploration of HY-2 in the living body and developing it as an anticancer drug.
Topics: Female; Humans; Antineoplastic Agents; Benzylisoquinolines; Breast Neoplasms; DNA; RecQ Helicases; RNA, Messenger; DNA Helicases
PubMed: 37988849
DOI: 10.1016/j.biopha.2023.115908 -
Journal of Stroke and Cerebrovascular... Jan 2024Bloom syndrome is a chromosomal breakage disorder associated with immune deficiency, characterized by short stature, predisposition to early-onset cancer, and immune...
OBJECTIVE
Bloom syndrome is a chromosomal breakage disorder associated with immune deficiency, characterized by short stature, predisposition to early-onset cancer, and immune defects. Currently, there have been no reports of acute cerebral infarction in patients with Bloom syndrome. Here, we report a case of Bloom syndrome complicated by elevated antiphospholipid antibodies and acute cerebral infarction.
MATERIALS AND METHODS
A 23-year-old male with a known genetic diagnosis of Bloom syndrome was admitted to the Respiratory Department due to pulmonary aspergillosis. The patient experienced sudden dizziness, and subsequent cranial MRI revealed a newly developed infarction in the right cerebellar hemisphere.
RESULTS
Six days later, the patient presented with sudden right visual field loss, and a repeat cranial MRI showed new infarctions in the left occipital and temporal lobes. Positive lupus anticoagulant and prolonged activated partial thromboplastin time suggested elevated antiphospholipid antibodies causing thrombus formation. Unfortunately, anticoagulant treatment was not administered due to recurrent hemoptysis.
CONCLUSION
This study reports the first case of a Bloom syndrome patient with elevated antiphospholipid antibodies and acute cerebral infarction, suggesting that the immune and coagulation abnormalities caused by Bloom syndrome may contribute to the development of acute cerebral infarction.
Topics: Male; Humans; Young Adult; Adult; Antibodies, Antiphospholipid; Ischemic Stroke; Bloom Syndrome; Antiphospholipid Syndrome; Stroke; Brain Ischemia; Infarction; Cerebral Infarction
PubMed: 37988834
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107490 -
JMIR Dermatology Oct 2023Congenital telangiectatic erythema (CTE), also known as Bloom syndrome, is a rare autosomal recessive disorder characterized by below-average height, a narrow face, a... (Review)
Review
BACKGROUND
Congenital telangiectatic erythema (CTE), also known as Bloom syndrome, is a rare autosomal recessive disorder characterized by below-average height, a narrow face, a red skin rash occurring on sun-exposed areas of the body, and an increased risk of cancer. CTE is one of many genodermatoses and photodermatoses associated with defects in DNA repair. CTE is caused by a mutation occurring in the BLM gene, which causes abnormal breaks in chromosomes.
OBJECTIVE
We aimed to analyze the existing literature on CTE to provide additional insight into its heredity, the spectrum of clinical presentations, and the management of this disorder. In addition, the gaps in current research and the use of artificial intelligence to streamline clinical diagnosis and the management of CTE are outlined.
METHODS
A literature search was conducted on PubMed, DOAJ, and Scopus using search terms such as "congenital telangiectatic erythema," "bloom syndrome," and "bloom-torre-machacek." Due to limited current literature, studies published from January 2000 to January 2023 were considered for this review. A total of 49 sources from the literature were analyzed.
RESULTS
Through this scoping review, the researchers were able to identify several publications focusing on Bloom syndrome. Some common subject areas included the heredity of CTE, clinical presentations of CTE, and management of CTE. In addition, the literature on rare diseases shows the potential advancements in understanding and treatment with artificial intelligence. Future studies should address the causes of heterogeneity in presentation and examine potential therapeutic candidates for CTE and similarly presenting syndromes.
CONCLUSIONS
This review illuminated current advances in potential molecular targets or causative pathways in the development of CTE as well as clinical features including erythema, increased cancer risk, and growth abnormalities. Future studies should continue to explore innovations in this space, especially in regard to the use of artificial intelligence, including machine learning and deep learning, for the diagnosis and clinical management of rare diseases such as CTE.
PubMed: 37796556
DOI: 10.2196/48413 -
Nature Communications Sep 2023The Boom syndrome helicase (BLM) unwinds a variety of DNA structures such as Guanine (G)-quadruplex. Here we reveal a role of RNF111/Arkadia and its paralog ARKL1, as...
The Boom syndrome helicase (BLM) unwinds a variety of DNA structures such as Guanine (G)-quadruplex. Here we reveal a role of RNF111/Arkadia and its paralog ARKL1, as well as Promyelocytic Leukemia Nuclear Bodies (PML NBs), in the regulation of ubiquitination and control of BLM protein levels. RNF111 exhibits a non-canonical SUMO targeted E3 ligase (STUBL) activity targeting BLM ubiquitination in PML NBs. ARKL1 promotes RNF111 localization to PML NBs through SUMO-interacting motif (SIM) interaction with SUMOylated RNF111, which is regulated by casein kinase 2 (CK2) phosphorylation of ARKL1 at a serine residue near the ARKL1 SIM domain. Upregulated BLM in ARKL1 or RNF111-deficient cells leads to a decrease of G-quadruplex levels in the nucleus. These results demonstrate that a CK2- and RNF111-ARKL1-dependent regulation of BLM in PML NBs plays a critical role in controlling BLM protein levels for the regulation of G-quadruplex.
Topics: Humans; Casein Kinase II; Promyelocytic Leukemia Nuclear Bodies; Promyelocytic Leukemia Protein; RecQ Helicases; Ubiquitination; Sumoylation; SUMO-1 Protein
PubMed: 37777511
DOI: 10.1038/s41467-023-41705-9