Assuntos
Ainhum/genética , Constrição Patológica/genética , Ceratodermia Palmar e Plantar/genética , Mutação de Sentido Incorreto/genética , Canais de Cátion TRPV/genética , Administração Tópica , Adulto , Ainhum/diagnóstico , Ainhum/patologia , Biópsia , Constrição Patológica/diagnóstico , Constrição Patológica/patologia , Cuba/epidemiologia , Feminino , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/tratamento farmacológico , Ceratodermia Palmar e Plantar/patologia , Ácido Láctico/administração & dosagem , Ácido Láctico/uso terapêutico , Linhagem , Canais de Cátion TRPV/metabolismo , Ureia/administração & dosagem , Ureia/uso terapêuticoRESUMO
Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the most devastating subtypes of epidermolysis bullosa, a group of skin and mucous membrane blistering disorders often associated with extracutaneous manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII collagen (C7), and to date over 700 different mutations in the 8835 nucleotides constituting the open reading frame or adjacent exon-intron boundaries of COL7A1 have been described. We used targeted next-generation sequencing to identify seven previously unreported mutations in a cohort of 17 Mexican patients who were diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our study expands the spectrum of mutations identified in this cohort, including those suitable for emerging therapies reliant on precise genotyping.
Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , MutaçãoAssuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Dermatopatias Vesiculobolhosas/genética , Adulto , Vesícula/patologia , Criança , Análise Mutacional de DNA , Epidermólise Bolhosa Distrófica/sangue , Epidermólise Bolhosa Distrófica/patologia , Feminino , Genes Recessivos , Humanos , Masculino , Mutação , Peru/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Dermatopatias Vesiculobolhosas/patologiaRESUMO
BACKGROUND: Gingival lesions in patients with dystrophic epidermolysis bullosa (DEB) are a common manifestation. However, their clinical features, frequency and severity are currently unknown. METHODS: Forty-five DEB patients were assessed by an oral medicine specialist, who analysed the presence/absence of four clinical signs (erythema, erosion/ulcer, atrophy, blister) on free and attached gingiva, using the Epidermolysis Bullosa Oropharyngeal Severity score. RESULTS: Twenty-eight (62.2%) out of 45 DEB patients showed different types of gingival lesions, whose presence/absence and total frequency/distribution were not significantly different between males and females (p=0.087 and p=0.091, respectively). Erythema was the most prevalent lesion (66.2%) and the recessive DEB severe generalized (RDEB-sev gen) reached the highest median disease activity score. A significant correlation was observed between the DEB subtypes and the disease activity median score (p<0.001), but not between age and total disease activity score in each group of DEB (p>0.05). Lastly, logistic regression showed that only gender (p=0.031) and RDEB-sev gen (p=0.001) were risks factors for the presence of gingival lesions. CONCLUSIONS: Gingival lesions in DEB patients are a relatively common entity and may have multiple clinical aspects, emphasizing the need for thorough attention and awareness among dentists.
Assuntos
Epidermólise Bolhosa Distrófica/patologia , Doenças da Gengiva/patologia , Adolescente , Adulto , Vesícula/patologia , Criança , Pré-Escolar , Estudos Transversais , Epidermólise Bolhosa Distrófica/classificação , Eritema/patologia , Feminino , Doenças da Gengiva/classificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Úlceras Orais/patologia , Atrofia Periodontal/patologia , Prevalência , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
Previous investigations have attempted to correlate the genotype with the cutaneous phenotype in patients with epidermolysis bullosa (EB), but never with the oropharyngeal phenotype. Seventeen dystrophic EB (DEB) patients were genotyped for COL7A1 gene mutations and divided into five distinct groups. Oropharyngeal disease severity was assessed with the Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score by an oral medicine specialist. The genotype-phenotype correlation was calculated by Kruskal-Wallis analysis of variance using the Mann-Whitney test, applying the Bonferroni correction. The most severe oropharyngeal phenotype was found in the group with the 2470insG/3948insT mutation, with a mean disease severity score of 18.50 ± 2.12; the mildest was found in the 6862del16 mutation group, with a mean disease severity score of 0.57 ± 1.13. The most significant difference in median score was found in the total score (P = 0.009), followed by tongue (P = 0.02) and upper lip (P = 0.021), but no correlation was found between disease severity and the groups (P>0.005, after Bonferroni correction). Multiple comparisons among the five different genotypic groups revealed no statistically significant genotype-oropharyngeal phenotype correlation; it was not possible to establish which group was more severe, or to associate a specific mutation to a specific oropharyngeal phenotype.
Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Doenças da Boca/genética , Adulto , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , México , Pessoa de Meia-Idade , Mutação , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease.
Assuntos
Hanseníase , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Vacina BCG , Vacinas Bacterianas , Quimioterapia Combinada , Saúde Global , Glicolipídeos/imunologia , Humanos , Testes Intradérmicos , Antígeno de Mitsuda , Hansenostáticos/administração & dosagem , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase/classificação , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/microbiologia , Mycobacterium leprae/imunologia , Mycobacterium leprae/isolamento & purificação , Mycobacterium leprae/fisiologia , Testes Sorológicos/métodos , Pele/microbiologia , Pele/patologia , Especificidade da EspécieRESUMO
A pair of 2-year-old female monozygotic twins presented with short and brittle hair. There was marked reduction in hair density, and excessive curving of the eyelashes. Onychodystrophy was also evident. They also had developmental delay in verbal and motor skills. Neither their parents nor other relatives were known to be affected, and there was no history of consanguinity. Examination of the hair shaft under light microscopy showed trichoschisis, which was more evident under electron microscopy. Under polarized light, the hair shafts showed the pathognomonic 'tiger-tail' pattern. The level of sulphur in the hair was low. Both patients were negative for TTDN1 mutation. Clinical correlation was performed and the diagnosis of Sabinas syndrome was made. Sabinas syndrome is a very rare autosomal recessive disorder first described in a group of patients from a small community in north-eastern Mexico. It is diagnosable at birth, and its major symptoms include brittle hair, mental retardation and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy.
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Doenças em Gêmeos/diagnóstico , Síndromes de Tricotiodistrofia/diagnóstico , Pré-Escolar , Doenças em Gêmeos/patologia , Feminino , Cabelo/ultraestrutura , Humanos , Síndromes de Tricotiodistrofia/classificação , Síndromes de Tricotiodistrofia/patologia , Gêmeos MonozigóticosRESUMO
We report a large Mexican kindred with a variant form of congenital universal hypertrichosis that is inherited in an apparent X-linked recessive manner. In addition to the generalized hypertrichosis, the affected individuals have dental malformations and deafness. Males are more severely affected than females who exhibit only mild hypertrichosis, but not deafness or dental anomalies. Haplotype analysis in this pedigree revealed linkage to a 13-cM region on chromosome Xq24-q27.1 between markers GATA198A10 and DXS8106. Localization of the gene underlying this form of hypertrichosis is the initial step in identifying genes on the X chromosome that are involved in the control of hair growth and development.
Assuntos
Cromossomos Humanos X , Surdez/genética , Ligação Genética , Hipertricose/congênito , Hipertricose/genética , Anormalidades Dentárias/genética , Mapeamento Cromossômico , Análise Mutacional de DNA , Feminino , Genes Recessivos , Genótipo , Haplótipos , Humanos , Masculino , México , Linhagem , FenótipoRESUMO
BACKGROUND: Type VII collagen gene (COL7A1) mutations are the cause of dystrophic epidermolysis bullosa (DEB), but most mutations are specific to individual families, and there are limited data on the nature of COL7A1 mutations in certain ethnic populations. OBJECTIVE: To determine the molecular basis of DEB in Hispanic Mexican patients. METHODS: Patients were recruited through a newly established support group, Fundacion DEBRA Mexico. Molecular analysis was performed by polymerase chain reaction (PCR) of genomic DNA using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. RESULTS: Fifty-nine of a possible 67 COL7A1 mutations (88%) were identified in 36 affected individuals (31 recessive, five dominant) in 21 families. Recessive mutations included six frameshift mutations, four silent glycine substitutions, and two splice-site mutations. Dominant mutations comprised a de novo glycine substitution and an internal deletion. Conclusions This study establishes the molecular basis of DEB in a group of Mexican patients. Only two of the mutations have been identified previously in other ethnic groups; the remainder are specific to this population. These new data are helpful in facilitating the accurate diagnosis of DEB subtype, in improving genetic counseling, and in providing further insight into the pathophysiology of this mechanobullous disease.
Assuntos
Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Dermatoses do Pé/genética , Dermatoses da Mão/genética , População Branca/genética , Adolescente , Adulto , Pré-Escolar , Primers do DNA , Epidermólise Bolhosa Distrófica/patologia , Feminino , Dermatoses do Pé/patologia , Dermatoses da Mão/patologia , Humanos , Joelho/patologia , Masculino , México , Mutação , Reação em Cadeia da PolimeraseRESUMO
A 32-basepair deletion polymorphism in the CCR5 chemokine receptor gene (DeltaCCR5) has recently been identified and shown to have functional significance in determining susceptibility to infection by human immunodeficiency virus type 1 (HIV-1) and a possible influence on disease progression in HIV-1-positive individuals. Interest has also focused on the geographical distribution of the DeltaCCR5 allele, particularly in considering epidemiological aspects of HIV disease and its impact on health economics. In this report we have assessed the frequency of the DeltaCCR5 allele in a Hispanic Mexican population and found a gene frequency of 4.4% in 103 individuals. The DeltaCCR5 allele is not present in indigenous Mexican populations but is present in about 8% of the population in Spain. Gene flow from the European gene pool consistent with Mexico's colonial past would account for the findings in this study.
Assuntos
Americanos Mexicanos/genética , Receptores CCR5/genética , Deleção de Sequência , Alelos , Frequência do Gene , Predisposição Genética para Doença , Infecções por HIV/genética , HIV-1 , HumanosRESUMO
Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). In this study, we determined the molecular basis of autosomal recessive DEB in a 19-year-old Hispanic Mexican woman by PCR amplification of genomic DNA, heteroduplex analysis, and automated sequencing of heteroduplex bandshifts. This approach revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and resulted in attenuated basement membrane zone expression of type VII collagen, a reduced number of anchoring fibrils at the dermal-epidermal junction, and a sub-lamina densa level of blister formation. Clinically, the patient had widespread trauma-induced skin fragility and complete loss of the nails, but had less pseudosyndactyly of the fingers and toes and milder mucosal involvement compared to most patients with the generalized form of this genodermatosis. We also screened 7 other Hispanic-Mexican patients with recessive DEB, none of whom were known to be related to this individual, for the mutation 2470insG using heteroduplex analysis and direct sequencing and detected this mutation on 7/14 alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms and microsatellite markers revealed that all the mutant alleles had arisen on similar allelic backgrounds, consistent with propagation of a common Hispanic Mexican ancestral haplotype. In view of the high allelic frequency of the mutation 2470insG in the patients studied, we recommend initial screening for this mutation when attempting to identify the molecular pathology of recessive DEB in Hispanic Mexican patients.
Assuntos
Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Éxons/genética , Adulto , Colágeno/análise , DNA/análise , DNA/genética , Epidermólise Bolhosa Distrófica/metabolismo , Saúde da Família , Feminino , Mutação da Fase de Leitura , Genes Recessivos , Análise Heteroduplex , Humanos , Imuno-Histoquímica , México , Linhagem , Pele/química , Pele/patologia , Pele/ultraestruturaRESUMO
Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). In this study, we assessed the molecular basis of recessive DEB in five affected individuals from two Mexican families. Both fathers of the affected children were first cousins. Genomic DNA was extracted from peripheral blood samples and assessed for COL7A1 mutations by polymerase chain reaction (PCR) amplification, heteroduplex analysis and direct automated sequencing of PCR products displaying heteroduplex bandshifts. In one family, we identified a homozygous 1 bp insertion of a G nucleotide in exon 19 of COL7A1, designated 2470insG, in three affected sisters. This mutation causes a frameshift and a premature termination codon on both alleles 178 bp downstream from the insertion; both parents were shown to be heterozygous carriers of this mutation. In the second family, the father of the other two affected children was also found to be a heterozygous carrier of this frameshift mutation. In addition, his unrelated partner was shown to be a heterozygous carrier of a different COL7A1 frameshift mutation, an insertion of a T nucleotide in exon 32, designated 3948insT. This mutation also results in a premature termination codon, 126 bp downstream from the insertion. Both affected children were compound heterozygotes for the 2470insG/3948insT mutations in COL7A1. Overall, these molecular findings offer a genetic explanation for the skin fragility in these related Mexican patients with recessive DEB. Immediate benefits from elucidation of the mutations include assessment of carrier status in other members of the family and the feasibility of DNA-based prenatal testing in subsequent pregnancies.
Assuntos
Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Mutação da Fase de Leitura , Adolescente , Adulto , Criança , Epidermólise Bolhosa Distrófica/patologia , Feminino , Genes Recessivos , Humanos , Masculino , México , Ácidos Nucleicos Heteroduplexes/genética , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). Nearly all cases of dominant DEB are caused by glycine substitution mutations occurring within the triple helical region of type VII collagen, and most of the mutations are unique to individual families. In this study, we identified a patient of Hispanic-Mexican origin with a mild form of DEB, which resulted from a de novo dominant glycine substitution, G2043R, in exon 73 of COL7A1. We also investigated a Scottish family with a three-generation pedigree of dominant DEB, in whom the same glycine to arginine substitution mutation was demonstrated. This particular mutation has also been detected previously in three other families with dominant DEB: one Italian, one Hungarian and one Norwegian. Given the widespread geographical distribution of this mutation and the demonstration of its occurrence as a de novo event, G2043R therefore represents the first example of a mutational hotspot in dominant DEB. Interestingly, although both the Mexican and Scottish families we studied had some clinical features in keeping with the Pasini form of the disorder, there was considerable interfamilial variability as well as intrafamilial diversity in the affected individuals.
Assuntos
Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Glicina/genética , Mutação Puntual/genética , Adulto , Pré-Escolar , Epidermólise Bolhosa Distrófica/patologia , Feminino , Análise Heteroduplex/métodos , Humanos , Masculino , México , Linhagem , Reação em Cadeia da Polimerase , Recidiva , Mapeamento por Restrição/métodos , EscóciaRESUMO
Las histiocitosis constituyen un grupo heterogéneo de enfermedades de causa desconocida y caracterizada por la presencia de histiocitos reactivos neoplásicos en varios tejidos y órganos. En su clasificación existe un grupo poco frecuente y conocido como histiocitocitosis de células de Langerhans cutánea pura autoinvolutiva. Se han descrito casos en todo el mundo y esta enfermedad se caracteriza por la proliferación de células de Langerhans con afección cutánea exclusiva y su tendencia a la curación espontánea. Presentamos dos casos clínicos