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Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Apr 2022Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS....
Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(=0.234,=0.023),palmoplantar keratoderma(=0.325,=0.001),webbing/pseudoainhum(=0.247,=0.016),dysphagia(=0.333,=0.001),urethral stricture(=0.280,=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(=11.292,=0.001)and anal stenosis(=4.014,=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).
Topics: Adolescent; Adult; Ainhum; Blister; Carcinoma, Squamous Cell; Child; Constriction, Pathologic; Deglutition Disorders; Epidermolysis Bullosa; Female; Humans; Inflammation; Keratoderma, Palmoplantar; Male; Membrane Proteins; Mutation; Neoplasm Proteins; Periodontal Diseases; Photosensitivity Disorders; Urethral Stricture; Young Adult
PubMed: 35538757
DOI: 10.3881/j.issn.1000-503X.14761 -
Cureus Apr 2024Kindler syndrome (KS) is a rare autosomal recessive skin condition. The FERMT1 gene mutates and causes symptoms such as blistering and epidermal atrophy, as well as an...
Kindler syndrome (KS) is a rare autosomal recessive skin condition. The FERMT1 gene mutates and causes symptoms such as blistering and epidermal atrophy, as well as an increased risk of cancer and poor wound healing. A male in his 20s sought treatment for his hyper-hypopigmentation over the body with poikiloderma of the face with thin wrinkled cigarette paper skin in association with photosensitivity. He gave a history of developing blisters all over the body during his childhood, which formed raw areas and eventually healed forming atrophic scars. The objective is to assess the correlation of clinical findings with dermoscopy in a case of KS. KS is a rare disorder with poikiloderma, photosensitivity, and acral bullae in infancy as predominant features. Dermoscopy proves to be a useful tool in the diagnosis of this rare disorder as it helps in the identification of poikiloderma, adermatoglyphia, and cigarette paper scarring.
PubMed: 38765347
DOI: 10.7759/cureus.58433 -
Proceedings of the Royal Society of... Jun 1947
Topics: Connective Tissue Diseases; Humans; Rothmund-Thomson Syndrome; Skin Diseases; Skin Neoplasms
PubMed: 19993586
DOI: No ID Found -
Experimental Dermatology May 2022Mutations in the human FAM111B gene are associated with a rare, hereditary multi-systemic fibrosing disease, POIKTMP. To date, there are ten POIKTMP-associated FAM111B... (Review)
Review
Mutations in the human FAM111B gene are associated with a rare, hereditary multi-systemic fibrosing disease, POIKTMP. To date, there are ten POIKTMP-associated FAM111B gene mutations reported in thirty-six patients from five families globally. To investigate the clinical significance of these mutations, we summarized individual cases by clinical features and position of the reported FAM111B gene mutations as those within and outside the putative protease domain (MWPPD and MOPPD respectively). MWPPD cases had more clinical manifestations than MOPPD (25 versus 18). Although the most common clinical features of poikiloderma, alopecia and hypohidrosis overall occurred in 94%, 86% and 75% of all cases with no significant differences between the MOPPD and MWPPD group, less common features included life-threatening (pulmonary fibrosis 47% vs. 13%; liver abnormalities specifically cirrhosis 26% vs. 7%) and physically disabling conditions (myopathy 53% vs. 20%; tendon contracture 55% vs. 7%) were more common in MWPPD cases. Similarly, the only 2 cases of POIKTMP with fatal pancreatic cancers were both only in the MWPPD group. This review thus suggests that mutations within the putative protease domain of the FAM111B protein are associated with a broader range of clinical features and may predict increased POIKTMP severity and a poorer prognosis.
Topics: Cell Cycle Proteins; Humans; Mutation; Peptide Hydrolases; Severity of Illness Index; Skin Diseases, Genetic
PubMed: 35122327
DOI: 10.1111/exd.14537 -
Proceedings of the Royal Society of... Dec 1932
PubMed: 19989031
DOI: No ID Found -
Indian Journal of Ophthalmology Jun 2020
Topics: Blister; Epidermolysis Bullosa; Humans; Periodontal Diseases; Photosensitivity Disorders
PubMed: 32461471
DOI: 10.4103/ijo.IJO_2261_19 -
Proceedings of the Royal Society of... Jan 1944
PubMed: 19992762
DOI: No ID Found -
FEBS Letters Jun 2013Recent studies from independent laboratories have decisively disclosed the identity of the long-sought 3-5' RNA exonuclease that trims posttranscriptionally the... (Review)
Review
Recent studies from independent laboratories have decisively disclosed the identity of the long-sought 3-5' RNA exonuclease that trims posttranscriptionally the oligouridine tail of U6, which is the small catalytic non-coding RNA promoting premRNA splicing within the spliceosome. This exonuclease, dubbed Mpn1 or Usb1, is a highly conserved enzyme that specifically removes uridines from the 3' end of U6, and directly generates terminal 2',3' cyclic phosphate groups. Mutations in the human gene encoding hMpn1 have been reported in patients diagnosed with the rare genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Mpn1-associated functions in U6 small nuclear RNA posttranscriptional regulation suggest the existence of sophisticated cellular pathways involved in surveillance and stabilization of U6. In this light, PN pathology might turn out to be a consequence of disturbed quality control of RNAs involved in crucial biological events.
Topics: Animals; Exoribonucleases; Humans; Phosphoric Diester Hydrolases; Protein Biosynthesis; RNA Stability
PubMed: 23684637
DOI: 10.1016/j.febslet.2013.05.005 -
Journal of Medical Case Reports Mar 2018Dermatomyositis is a humoral-mediated inflammatory myopathy with symmetrical proximal muscle weakness and dermatological manifestations such as Gottron's papules,...
BACKGROUND
Dermatomyositis is a humoral-mediated inflammatory myopathy with symmetrical proximal muscle weakness and dermatological manifestations such as Gottron's papules, heliotrope rash, periungual abnormalities, and flagellate erythema. Erythroderma is a severe and potentially life-threatening dermatological condition with diffuse erythema and scaling involving more than 90% of the skin surface area. Poikiloderma vasculare atrophicans refers to mottled hyperpigmentation and hypopigmentation of the skin with in-between telangiectases and areas of atrophy and is considered a variant of mycosis fungoides. Poikilodermatomyositis is the term given to the condition with poikiloderma and inflammatory myopathy. Only a few cases are reported on erythroderma in dermatomyositis and poikilodermatomyositis. Erythrodermal pattern of dermatomyositis transforming into poikilodermatomyositis is a recognized rare manifestation of dermatomyositis and we could find only one case report in the literature.
CASE PRESENTATION
A 53-year-old Sri Lankan woman presented with intermittent fever of 5 months' duration with erythroderma. Later she developed progressive, symmetrical proximal muscle weakness. Following a short course of small dose steroids, erythroderma settled but changed to extensive poikiloderma involving more than 90% of her skin with her face being relatively spared. She had an early heliotrope rash, shawl sign, and Gottron papules. Electromyography and muscle biopsy were supportive of inflammatory myositis and skin biopsy showed evidence of dermatomyositis. Inflammatory markers and muscle enzymes were also elevated. Autoimmune antibodies and myositis-specific autoantibodies were negative. She was started on orally administered prednisolone 1 mg/kg per day with methotrexate 10 mg once a week and had a good response to treatment with resolution of the skin condition and improvement of muscle power. Imaging studies, endoscopies, and tumor markers did not reveal any malignancy.
CONCLUSIONS
This case illustrates a rare presentation of dermatomyositis initially presenting as fever, erythroderma, and proximal muscle weakness and later developing poikiloderma involving more than 90% of the skin. It is important to be aware of this rare presentation to avoid misdiagnosis. With the currently available literature it is not possible to conclude that erythroderma is a bad prognostic factor in dermatomyositis or a predictive factor for a malignancy. Patients have a good response to steroids with a combination of immunosuppressants.
Topics: Dermatologic Agents; Dermatomyositis; Electromyography; Female; Fever; Humans; Methotrexate; Middle Aged; Muscle Weakness; Neutropenia; Prednisolone; Skin Abnormalities; Treatment Outcome
PubMed: 29571300
DOI: 10.1186/s13256-018-1618-y -
The Journal of Investigative Dermatology Feb 2019Kindler syndrome is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding t kindlin-1. Kindlin-1 localizes to focal adhesion and...
Kindler syndrome is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding t kindlin-1. Kindlin-1 localizes to focal adhesion and is known to contribute to the activation of integrin receptors. Most cases of Kindler syndrome show a reduction or complete absence of kindlin-1 in keratinocytes, resulting in defective integrin activation, cell adhesion, and migration. However, roles for kindlin-1 beyond integrin activation remain poorly defined. In this study we show that skin and keratinocytes from Kindler syndrome patients have significantly reduced expression levels of the EGFR, resulting in defective EGF-dependent signaling and cell migration. Mechanistically, we show that kindlin-1 can associate directly with EGFR in vitro and in keratinocytes in an EGF-dependent, integrin-independent manner and that formation of this complex is required for EGF-dependent migration. We further show that kindlin-1 acts to protect EGFR from lysosomal-mediated degradation. This shows a new role for kindlin-1 that has implications for understanding Kindler syndrome disease pathology.
Topics: Blister; Cell Line; Cell Movement; EGF Family of Proteins; Epidermolysis Bullosa; ErbB Receptors; Humans; Keratinocytes; Lysosomes; Membrane Proteins; Neoplasm Proteins; Periodontal Diseases; Photosensitivity Disorders; Proteolysis; Signal Transduction; Skin
PubMed: 30248333
DOI: 10.1016/j.jid.2018.08.020