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Frontiers in Cell and Developmental... 2023Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the gene that encodes a nuclear trypsin-like serine protease....
Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterized the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though -deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. When mutated as in HFP, FAM111B was more frequently localized to the nuclear envelope, suggesting that accumulation of the mutated protease at the nuclear periphery may drive the disease pathology.
PubMed: 37342232
DOI: 10.3389/fcell.2023.1175069 -
Journal of Cosmetic Dermatology Jun 2023Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser...
INTRODUCTION
Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser therapy has emerged as a viable treatment option for these vascular anomalies.
MATERIALS AND METHODS
Although there are several types of lasers, the 1064-nm Nd:YAG in particular is popularly selected for its safety profile and versatility. The longer 1064 nm wavelength penetrates deeper into the skin while also being less absorbed by hemoglobin and melanin, thus resulting in minimized damage to surrounding structures and less pigmentation changes. The new LP1064 applicator on the Harmony XL Pro Device is one such laser.
RESULTS
Numerous publications have corroborated the efficacy of 1064 nm Nd:YAG lasers. These studies cite at least over 75% of patients experiencing significant improvement in common vascular lesions. Efficacy of this laser is also seen for other vascular lesions such as port wine stains, hemangiomas, venous lakes, poikiloderma of Civatte, and angiokeratomas. Overall, the reported studies also show a low incidence of adverse events.
CONCLUSION
The 1064 nm Nd:YAG laser, such as the Harmony LP1064 applicator, is a safe and effective tool to treat vein anomalies of the face and leg. Although commonly used for vein ablation, it has demonstrated a robust response in other indications as well.
Topics: Humans; Telangiectasis; Veins; Port-Wine Stain; Laser Therapy; Low-Level Light Therapy; Lasers, Solid-State; Treatment Outcome
PubMed: 37318789
DOI: 10.1111/jocd.15756 -
Annals of Medicine and Surgery (2012) May 2023Kindler syndrome is a rare autosomal recessive inherited disease. The authors report a case with unique presentation that has never reported before in the medical...
Kindler syndrome is a rare autosomal recessive inherited disease. The authors report a case with unique presentation that has never reported before in the medical Literatur" lanugo hair". This is a case of a 13-year-old Syrian child, who presented with difuse fine face hair, and serious urinary complications. Kindler syndrome is characterized by acral skin blistering beginning at birth, diffuse cutaneous atrophy, photosensitivity, poikiloderma, and various mucosal findings. Highlighting a set of clinical diagnostic criteria; which is used only if a genetic test is not available.
PubMed: 37229095
DOI: 10.1097/MS9.0000000000000503 -
Blood Science (Baltimore, Md.) Apr 2023Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder with clinical features consisting of rash, poikiloderma, sparse hair, short stature, juvenile...
Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder with clinical features consisting of rash, poikiloderma, sparse hair, short stature, juvenile cataracts, skeletal abnormalities, and cancer predisposition. Genetic studies involving detection of pathogenic variants provide the diagnostic certitude. Osteosarcoma was found in two-thirds -mutated RTS patients, while hematological malignancies were rarely reported. The variant diversity of gene has not been fully identified and mutations associated with hematologic malignancies are not well described. In this study, we presented a pedigree of RTS from a Chinese family, among which the proband was diagnosed with de novo myelodysplastic syndrome (MDS). Comprehensive medical examination and chromosome karyotyping were performed on the proband. Whole exome sequencing (WES) was performed on the proband, his sister and his mother. The familial cosegregation of sequence variants derived from WES was conducted by polymerase chain reaction-based Sanger sequencing. Structures of candidate RECQL4 mutants were done by in silico analysis to assess pathogenicity. Three novel germline variants, including c.T274C, c.G3014A, and c.G801C, were identified by WES and validated by Sanger sequencing. Prediction of conformation indicated that the structural stability of human RECQL4 protein was largely affected with these variants. The co-occurring p.S34F and p.Y220C mutations might contribute to the development of MDS. Our study expands the mutational spectrum of and provides underlying molecular mechanism for the development of MDS in RTS patients.
PubMed: 37228773
DOI: 10.1097/BS9.0000000000000152 -
International Journal of General... 2023FAM111B (FAM111 trypsin-like peptidase B) gene mutations have been linked to a hereditary fibrosing poikiloderma disorder known to cause poikiloderma, tendon...
INTRODUCTION
FAM111B (FAM111 trypsin-like peptidase B) gene mutations have been linked to a hereditary fibrosing poikiloderma disorder known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). Overexpression of FAM111B has been associated with an increased risk of certain cancers with a poor prognosis, although the relationship between FAM111B and other tumors is still unclear, and the molecular mechanism of its action is not fully understood.
METHODS
We investigated the biological functions of FAM111B in 33 solid tumors using multi-omics data. We further recruited 109 gastric cancer (GC) patients for a clinical cohort study to confirm the effect of FAM111B on early tumor recurrence. Furthermore, we assessed the role of FAM111B in GC cell proliferation and migration via EdU incorporation, CCK8 and transwell assays in vitro.
RESULTS
We found that FAM111B can enhance oncogenesis and progression in multiple tumor types. The clinical cohort of GC showed that upregulation of FAM111B is associated with early recurrence of GC, and knockdown of the FAM111B gene can inhibit the proliferation and migration of GC cells. Gene enrichment analysis indicates that FAM111B promotes cancer through immune system process, chromosome instability, DNA repair, and apoptosis regulation. Mechanistically, FAM111B appears to promote the growth cycle of malignant tumor cells while inhibiting apoptosis.
CONCLUSION
FAM111B may serve as a potential pan-cancer biomarker for predicting the prognosis and survival of malignant tumor patients. Our study elucidates the role of FAM111B in the occurrence and development of various cancers, and highlights the need for future research on FAM111B in cancers.
PubMed: 37213474
DOI: 10.2147/IJGM.S409690 -
Journal of Medical Genetics Nov 2023Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I,...
Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in and juvenile cataracts, and type II, with biallelic variants in , increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in , with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of mutations, incorporating clinical characteristics of RTS. Although a clear genotype-phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of -related syndromes.
PubMed: 37055165
DOI: 10.1136/jmg-2022-109119 -
Genetics in Medicine : Official Journal... Jul 2023Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma, sparse hair, small stature, skeletal defects, cancer, and cataracts, resembling features of premature...
PURPOSE
Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma, sparse hair, small stature, skeletal defects, cancer, and cataracts, resembling features of premature aging. RECQL4 and ANAPC1 are the 2 known disease genes associated with RTS in >70% of cases. We describe RTS-like features in 5 individuals with biallelic variants in CRIPT (OMIM 615789).
METHODS
Two newly identified and 4 published individuals with CRIPT variants were systematically compared with those with RTS using clinical data, computational analysis of photographs, histologic analysis of skin, and cellular studies on fibroblasts.
RESULTS
All CRIPT individuals fulfilled the diagnostic criteria for RTS and additionally had neurodevelopmental delay and seizures. Using computational gestalt analysis, CRIPT individuals showed greatest facial similarity with individuals with RTS. Skin biopsies revealed a high expression of senescence markers (p53/p16/p21) and the senescence-associated ß-galactosidase activity was elevated in CRIPT-deficient fibroblasts. RECQL4- and CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors and no or only mild sensitivity to genotoxic stress by ionizing radiation, mitomycin C, hydroxyurea, etoposide, and potassium bromate.
CONCLUSION
CRIPT causes an RTS-like syndrome associated with neurodevelopmental delay and epilepsy. At the cellular level, RECQL4- and CRIPT-deficient cells display increased senescence, suggesting shared molecular mechanisms leading to the clinical phenotypes.
Topics: Humans; Rothmund-Thomson Syndrome; Cellular Senescence; DNA Damage; Hydroxyurea; Fibroblasts; Mutation; Adaptor Proteins, Signal Transducing
PubMed: 37013901
DOI: 10.1016/j.gim.2023.100836 -
PLOS Global Public Health 2023There is still a lack of research in Vietnam on the autoantibody profile of dermatomyositis (DM) and its association with clinical and subclinical characteristics....
There is still a lack of research in Vietnam on the autoantibody profile of dermatomyositis (DM) and its association with clinical and subclinical characteristics. Therefore, we conducted this study to investigate clinical and subclinical correlations with autoantibodies in DM patients. 72 DM patients at Vietnam National Hospital of Dermatology and Venereology (NHDV) from March 2019 to September 2021 were included in this cross-sectional study. Clinical manifestations and laboratory test results of the patients were obtained at the time of visit. Of these, 63 patients were tested for the presence of autoantibodies using an Immunoblot assay. Our findings show that the average age of patients was 41.7 years. The female-male ratio was 1.7:1. The most common skin and muscle manifestations were myalgia (79.2%), heliotrope rash (62.5%), shawl sign (61.1%), Gottron's sign (59.7%), muscle weakness (59.7%), Gottron's papule (52.8%), periungual telangiectasia (41.7%), V-sign (38.9%), poikiloderma (26.4%), periungual fissures (20.8%), Raynaud's phenomenon (15.3%). Among the 63 patients tested for autoantibodies, myositis-specific antibodies (MSAs) were found in 71.4% of the serum samples, and myositis-associated antibodies (MAAs) in 36.5%. Anti-TIF1γ antibody accounted for the highest percentage (28.6%), followed by anti-Ro52 (22.2%), anti-synthetase (17.5%), anti-Mi-2 and anti-MDA5 (both 14.3%). Anti-synthetase antibodies (ARS-Abs) showed a significant association with arthralgia, fever, and Raynaud's phenomenon, while anti-TIF1γ antibodies showed a strong association with V-sign and poikiloderma (p<0.05). Clinical features in dermatomyositis are heterogeneous. Our study results show some associations between clinical features and autoantibodies in patients with DM. The analysis of DM-related autoantibodies is clinically useful, will be essential for the approaches to diagnosis, and management of DM patients.
PubMed: 36962887
DOI: 10.1371/journal.pgph.0000979 -
The Journal of Dermatology Sep 2023
Topics: Female; Humans; East Asian People; Mutation; Neutropenia; Phosphoric Diester Hydrolases; Skin Abnormalities; Siblings
PubMed: 36938655
DOI: 10.1111/1346-8138.16782 -
Revista Paulista de Pediatria : Orgao... 2023The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early...
OBJECTIVE
The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early diagnosis in patients with xeroderma pigmentosum (XP).
CASE DESCRIPTION
An 8-year-old male patient was referred to the Joana de Gusmão Hospital (HIJG) in 2021 for evaluation and specialized care. Previously, the child was followed in his place of origin by oncologic and palliative care, where he was submitted to surgeries and chemotherapy. He was admitted to the HIJG using vismodegib, acitrein, tramadol, and solar protective measures. On physical examination, there were tumors and disseminated macular verrucous and ulcerated lesions. The imaging examination showed solid and expansive lesions on the face, and atelectasis and fibroscarring changes in the lung. The histopathological report proved the existence of melanocanthoma, carcinoma, and pyogenic granuloma. After the evaluation of the case, no surgery, chemotherapy, or radiotherapy was performed. It was decided to maintain the palliative treatment and to continue the use of tramadol for pain, and vismodegib and acitretin were used to control carcinomas and prophylactic measures.
COMMENTS
The XP is a rare disease of autosomal recessive inheritance whose mechanism comes from failure in the DNA repair by exposure to ultraviolet rays, resulting in lesions on the skin and mucous membranes. They start as sunburns and can progress to melanosis, areas with altered pigmentation, premature aging, poikiloderma, and areas of high risk for neoplasms.
Topics: Child; Male; Humans; Xeroderma Pigmentosum; Tramadol; DNA Repair; Skin Diseases; Carcinoma; Skin Neoplasms
PubMed: 36921168
DOI: 10.1590/1984-0462/2023/41/2021390