-
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 -
The Journal of Investigative Dermatology Nov 2016Kindler syndrome (KS) is an autosomal recessive blistering skin disease resulting from pathogenic mutations in FERMT1. This gene encodes kindlin-1, a focal adhesion...
Kindler syndrome (KS) is an autosomal recessive blistering skin disease resulting from pathogenic mutations in FERMT1. This gene encodes kindlin-1, a focal adhesion protein involved in activation of the integrin family of extracellular matrix receptors. Most cases of KS show a marked reduction or complete absence of the kindlin-1 protein in keratinocytes, resulting in defective cell adhesion and migration. Electric fields also act as intrinsic regulators of adhesion and migration in the skin, but the molecular mechanisms by which this occurs are poorly understood. Here we show that keratinocytes derived from KS patients are unable to undergo electrotaxis, and this defect is restored by overexpression of wild-type kindlin-1 but not a W612A mutation that prevents kindlin-integrin binding. Moreover, deletion of the pleckstrin homology domain of kindlin-1 also failed to rescue electrotaxis in KS cells, indicating that both integrin and lipid binding are required for this function. Kindlin-1 was also required for the maintenance of lamellipodial protrusions during electrotaxis via electric field-activated β1 integrin. Indeed, inhibition of β1 integrins also leads to loss of electrotaxis in keratinocytes. Our data suggest that loss of kindlin-1 function may therefore result in epithelial insensitivity to electric fields and contribute to KS disease pathology.
Topics: Blister; Cell Adhesion; Cell Proliferation; DNA; DNA Mutational Analysis; Epidermolysis Bullosa; Humans; Keratinocytes; Membrane Proteins; Mutation; Neoplasm Proteins; Periodontal Diseases; Photosensitivity Disorders; Skin
PubMed: 27427485
DOI: 10.1016/j.jid.2016.05.129 -
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 -
Frontiers in Oncology 2022gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In... (Review)
Review
gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In addition, the overexpression of FAM111B has been associated with cancer progression and poor prognosis. This review inferred the molecular function of this gene's protein product and mutational dysfunction in fibrosis and cancer based on recent findings from studies on this gene. In conclusion, FAM111B represents an uncharacterized protease involved in DNA repair, cell cycle regulation, and apoptosis. The dysregulation of this protein ultimately leads to fibrotic diseases like POIKTMP and cancers the disruption of these cellular processes by the mutation of the gene. Hence, it should be studied in the context of these diseases as a possible therapeutic target.
PubMed: 35860584
DOI: 10.3389/fonc.2022.932167 -
Dermatology Practical & Conceptual Jan 2023Poikiloderma of Civatte (PC) is a common, acquired, chronic, benign poikiloderma of the neck and face, most commonly affecting peri-menopausal females. At the time of...
INTRODUCTION
Poikiloderma of Civatte (PC) is a common, acquired, chronic, benign poikiloderma of the neck and face, most commonly affecting peri-menopausal females. At the time of writing, few studies have been published regarding the dermoscopy of PC.
OBJECTIVE
To describe the dermoscopic picture of PC, so as to provide a clinico dermoscopic diagnosis and differential diagnosis for PC.
METHODS
Twenty-eight patients with PC, aged 26-73 years, of whom 19 females (67.86%) were evaluated by detailed history, clinical examination, and dermoscopic examination with hand-held dermoscope.
RESULTS
The reticular pattern was observed in 15 cases (53.6%); the white dot in 10 (35.7%); the non-specific in 9 (32.1%); and the combination of linear and dotted vessels in 8 (28.6%). Regarding local dermoscopic features, converging curved vessels were observed in 18 cases (64.3%); linear irregular vessels in 17 (60.7%); rhomboidal/polygonal vessels in 15 (53.6%); dotted/globular vessels in 10 (35.7%); white macules in 23 (82.1%); brown macules in 11 (39.3%); and whitish follicular plugs in 6 (21.4%).
CONCLUSIONS
The dermoscopic picture of PC is highly characteristic and corresponds well to both clinical and histological findings. Dermoscopy may assist clinical diagnosis, as well as the differentiation from other dermatoses of the neck and face, especially poikilodermas with guarded prognosis.
PubMed: 36892344
DOI: 10.5826/dpc.1301a7 -
Actas Dermo-sifiliograficas Nov 2020Kindler syndrome is a very rare form of bullous epidermolysis. It is a hereditary condition caused by a mutation in the FERMT1 gene that encodes the protein kindlin-1....
Kindler syndrome is a very rare form of bullous epidermolysis. It is a hereditary condition caused by a mutation in the FERMT1 gene that encodes the protein kindlin-1. It is clinically characterized by trauma-induced blistering, diffuse skin atrophy, poikiloderma, pseudosyndactyly, and photosensitivity. The most common mucosal manifestations are conjunctivitis, ectropion, hemorrhagic gingivitis, periodontal disease, premature tooth loss, and severe colitis. We present the first 4 cases of Kindler syndrome diagnosed at the Instituto Nacional de Salud del Niño in Lima, Peru. These cases highlight the unique clinical presentation and multiple manifestations of this disease and show how a multidisciplinary management approach kept symptoms under control and significantly improved patient quality of life.
Topics: Blister; Epidermolysis Bullosa; Humans; Membrane Proteins; Neoplasm Proteins; Periodontal Diseases; Peru; Photosensitivity Disorders; Quality of Life
PubMed: 32861675
DOI: 10.1016/j.ad.2019.04.013 -
Dermatology Practical & Conceptual Jul 2022Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the...
INTRODUCTION
Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the naked eye. Recently, it gained popularity for evaluation of inflammatory skin conditions. In the field of connective tissue diseases, dermoscopy has been used mainly as a simple and accessible substitute of nailfold capillaroscopy.
OBJECTIVES
The aim of the present study is to expand the application of dermoscopy in patients with dermatomyositis (DM) beyond the usual nailfold examination. A clinico-dermoscopic correlation between clinical signs of skin affection and dermoscopic features is also suggested.
METHODS
A total of 29 patients with DM were enrolled in this descriptive prospective study, conducted over a 3-year period. Dermoscopy was performed by a DermLite DL1 dermatoscope on polarization mode, attached to One Plus 3T camera. The following skin lesions were examined: periungual affection, scalp DM, Gottron papules, palmar papules, poikiloderma and auricular changes.
RESULTS
Dermoscopy detected predominantly advanced nail fold capillary changes - giant capillaries (79%), microhemorrhages (46%) and avascular areas (25%). The most prevalent trichoscopic features were enlarged tortuous capillaries (64%), interfollicular scales (50%) and peripilar casts and tufting (36%). Among the other skin lesions assessed in this study - Gottron papules were present in 20 patients, poikiloderma in 11, palmar papules in 4 and auricular lesions in 4 patients.
CONCLUSIONS
The use of dermoscopy for clinical evaluation of skin lesions in DM enhances diagnostic accuracy and elucidates poorly known characteristics of the disease.
PubMed: 36159137
DOI: 10.5826/dpc.1203a142 -
Frontiers in Genetics 2022Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and...
Case Report: Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia.
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids. A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and heterozygous missense mutation, c.1886T > G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid. We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease.
PubMed: 35601499
DOI: 10.3389/fgene.2022.870192 -
Proceedings of the Royal Society of... Mar 1932
PubMed: 19988612
DOI: No ID Found -
Case Reports in Dermatology May 2014Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder presenting with poikiloderma and other clinical features, affecting the bones and eyes and, in...
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder presenting with poikiloderma and other clinical features, affecting the bones and eyes and, in type II RTS, presenting an increased risk for malignancy. With about 300 cases reported so far, we present a 13-year follow-up including clinical images, X-rays and genetic analysis. A 13-month-old female started with a facial rash with blisters on her cheeks and limbs at the age of 3 months along with congenital hypoplastic thumbs, frontal bossing and fine hair, eyebrows and eyelashes. The patient was lost to follow-up and returned 12 years later with palmoplantar hyperkeratotic lesions, short stature, disseminated poikiloderma and sparse scalp hair, with absence of eyelashes and eyebrows. Radiographic analysis showed radial ray defect, absence of the thumb and three wrist carpal bones, and reduced bone density. Gene sequencing for the RECQL4 helicase gene revealed a mutation on each allele. RTS is a rare disease, and in this patient we observed the evolution of her skin lesions and other clinical features, which were important for the classification of type II RTS. The next years will provide even more information on this rare disease.
PubMed: 25120469
DOI: 10.1159/000365625