RESUMO
To aid in the standardization of evaluating patients with multiple keloids, a Keloid Area and Severity Index (KASI) was developed using patient feedback, previous literature, and clinical expertise. The system was validated using intrarater and interrater reliability assessments. Here, we present a verified, reliable method of assessing keloid area and severity in clinical and research settings.
Assuntos
Queloide , Humanos , Queloide/diagnóstico , Queloide/patologia , Reprodutibilidade dos TestesRESUMO
CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.
Assuntos
Craniossinostoses , Anormalidades do Sistema Digestório , Poroceratose , RNA Nuclear Pequeno/genética , Canal Anal/anormalidades , Craniossinostoses/genética , Humanos , Splicing de RNA , RNA Nuclear Pequeno/químicaRESUMO
We present a severe case of acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole complicated by non-infectious circulatory shock in a 16-year-old boy. Hemodynamic instability has been reported as a complication of AGEP in adults, but is rarely observed in pediatric patients. The patient we present demonstrated characteristic cutaneous findings of AGEP including isolated non-follicular, sterile pustules on a background of erythema with involvement at intertriginous areas and subsequently developed non-infectious circulatory shock. This case expands the spectrum of possible clinical presentations for AGEP in pediatric patients.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Adolescente , Adulto , Criança , Humanos , MasculinoAssuntos
Alopecia , Dermatite , Humanos , Estudos Retrospectivos , Alopecia/complicações , Alopecia/epidemiologia , Couro CabeludoRESUMO
The discovery that oxidized vitamin C, dehydroascorbate (DHA), can induce oxidative stress and cell death in cancer cells has rekindled interest in the use of high dose vitamin C (VC) as a cancer therapy. However, high dose VC has shown limited efficacy in clinical trials, possibly due to the decreased bioavailability of oral VC. Because human erythrocytes express high levels of Glut1, take up DHA, and reduce it to VC, we tested how erythrocytes might impact high dose VC therapies. Cancer cells are protected from VC-mediated cell death when co-cultured with physiologically relevant numbers of erythrocytes. Pharmacological doses of VC induce oxidative stress, GSH depletion, and increased glucose flux through the oxidative pentose phosphate pathway (PPP) in erythrocytes. Incubation of erythrocytes with VC induced hemolysis, which was exacerbated in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD) patients and rescued by antioxidants. Thus, erythrocytes protect cancer cells from VC-induced oxidative stress and undergo hemolysis in vitro, despite activation of the PPP. These results have implications on the use of high dose VC in ongoing clinical trials and highlight the importance of the PPP in the response to oxidative stress.
Assuntos
Ácido Ascórbico/efeitos adversos , Eritrócitos/citologia , Glutationa/metabolismo , Neoplasias/metabolismo , Estresse Oxidativo , Via de Pentose Fosfato , Ácido Ascórbico/metabolismo , Linhagem Celular Tumoral , Ácido Desidroascórbico/efeitos adversos , Ácido Desidroascórbico/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Neoplasias/enzimologia , Neoplasias/genética , Oxirredução , Estresse Oxidativo/efeitos dos fármacosRESUMO
Keloids are an exuberant response to cutaneous wound healing. Several lines of evidence suggest that keloid scarring is influenced by genetic factors. This review will discuss our current understanding of genetic influences on keloidal scarring via familial inheritance patterns; ethnic differences in prevalence; syndromes with keloid occurrence; linkage analysis, genome-wide association studies, and admixture mapping studies; transforming growth factor beta and p53 variant studies; and human leukocyte antigen polymorphisms.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Queloide/genética , Povo Asiático/genética , População Negra/genética , Epigênese Genética , Antígenos HLA/genética , Humanos , Cicatrização/genéticaRESUMO
Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development.
Assuntos
Displasia Ectodérmica/genética , Proteínas de Homeodomínio/genética , Mutação de Sentido Incorreto/genética , Displasia Ectodérmica/patologia , Humanos , Lactente , Masculino , LinhagemAssuntos
Procedimentos Cirúrgicos Dermatológicos , Queloide/prevenção & controle , Pentoxifilina/administração & dosagem , Prevenção Secundária/métodos , Administração Oral , Adulto , Idoso , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Queloide/epidemiologia , Queloide/cirurgia , Masculino , Pessoa de Meia-Idade , Pentoxifilina/efeitos adversos , Projetos Piloto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Multiple primary milia were found on the vulva of a 52-year-old woman who was referred to the dermatology clinic by her gynecologist. These lesions are commonly distributed on the face and rarely occur in this location without antecedent trauma. This report demonstrates the unique presentation of primary milia in the genital region and explores the diagnostic features and treatment methods of these lesions.