RESUMO
BACKGROUND: The incidence of skin cancer has reached epidemic proportions in the white population and is significantly elevated in agricultural populations, who are exposed to ultraviolet radiation during their professional activities. In 2014, the Agricultural Social Insurance Mutual Benefit Fund (MSA) offered its customers who work in agriculture and live in rural areas with reduced access to dermatologists the ability to participate in a 1-day teledermoscopic (TDS) screening event. OBJECTIVE: This study's aim was to assess the feasibility of real-time mobile TDS triage of a large number of agricultural workers by trained medical officers and occupational physicians. METHODS: Fifteen TDS screening centres were located in different areas of France. Individuals older than 18 years who worked in agriculture and lived in rural area near a TDS screening centre were invited to participate in a 1-day screening event and were examined by an MSA physician. In cases of suspicious skin lesions, clinical and dermoscopic images were obtained and transferred immediately to four dermatologists who were simultaneously present at the tele-platform for diagnosis and decision-making. Low-quality images were retaken. RESULTS: Two-hundred eighty-nine patients underwent skin cancer screening. Among 199 patients (69%), 390 suspicious lesions were identified and generated 412 pictures. All lesions were analysed by dermatologists. For 105 patients (53%), no follow-up was required. Seventeen patients were referred to local dermatologists for rapid examination, including 12 cases of suspected malignant melanocytic lesions. Among the 12 patients with suspected melanoma, face-to-face visits were conducted within 10 days for 11 of them, and 1 case of melanoma was confirmed by histopathology. CONCLUSIONS: Our study suggests that teledermoscopy performed in the context of occupational medicine and targeted to agricultural populations is feasible and could be useful for improving skin cancer screening in at-risk populations while avoiding face-to-face examinations by a dermatologist in 53% of cases.
Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Telefone Celular , Dermoscopia , Neoplasias Cutâneas/diagnóstico , Telemedicina , Doenças dos Trabalhadores Agrícolas/epidemiologia , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Unidades Móveis de Saúde , Neoplasias Cutâneas/epidemiologiaRESUMO
BACKGROUND: Ainhum, or spontaneous dactylitis, involves the formation of a gradual constriction in the digital-plantar fold of the fifth toe that leads, after several years, to autoamputation of the digit. This condition is classically distinguished from "true" ainhum, of unknown aetiology and affecting only subjects of African origin, from "pseudo-ainhum", resulting from different causes such as inflammatory constriction or constriction by a foreign body, and finally from ainhumoid palmoplantar keratoderma, which is of genetic origin and occurs for instance in Vohwinkel syndrome. Herein, we report three cases of ainhum in women of sub-Saharan African origin; in addition, all three subjects were also presenting various forms of hyperkeratosis of the hands and feet known to primarily affect subjects of African origin. PATIENTS AND METHODS: The three patients, aged 30, 48 and 44 years, were respectively from Mali, Guinea and Senegal. They had consulted a dermatologist for violent pain in the fifth toe, which frequently prevented sleep and was inexplicable despite several consultations, and even in one case in spite of surgical investigation. Once the diagnosis had been made, relief was promptly provided for all three patients through Z-plasty to remove the circular constriction around the toe in question. In addition to ainhum, the first patient was also presenting diffuse palmoplantar keratoderma, together with an aspect of acrokeratoelastoidosis on the edges of her hands and feet, and knuckle pads, while the second was presenting diffuse palmoplantar keratoderma and an aspect of marginal acrokeratoelastoidosis, and the third was presenting small knuckle pads. DISCUSSION: A recent study has confirmed the high incidence of several forms of palmoplantar keratoderma of African origin, as well as frequent association of these different varieties with one another. These consist of diffuse keratoderma having a relatively non-specific aspect, keratoderma punctata of the palmar creases, marginal keratoderma known also as focal acral hyperkeratosis, and acrokeratoelastoidosis, despite the absence of histological evidence, and finally, inverted keratoderma, i.e. affecting the dorsal aspects of the extremities, such as knuckle pads. In the three cases presented here, ainhum was associated with these different forms of acral keratoderma seen chiefly in subjects of African origin. CONCLUSION: So-called "true" ainhum may be included in a broader group of African acral keratoderma, further reinforcing the unity of this group. Genetic studies are required to enable validation and refinement of these clinical findings.
Assuntos
Ainhum/etiologia , Ceratodermia Palmar e Plantar/complicações , Adulto , População Negra , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a life-threatening autosomal disease characterized by loss of dermal-epidermal adherence with abnormal anchoring fibrils (AF). We recently linked HS-RDEB to the type VII collagen gene (COL7A1) which encodes the major component of AF. We describe a patient who is homozygous for an insertion-deletion in the FN-4A domain of the COL7A1 gene. This defect causes a frameshift mutation which leads to a premature stop codon in the FN-5A domain, resulting in a marked diminution in mutated mRNA levels, with no detectable type VII collagen polypeptide in the patient. Our data suggest strongly that this null allele prevents normal anchoring fibril formation in homozygotes and is the underlying cause of HS-RDEB in this patient.
Assuntos
Colágeno/genética , Elementos de DNA Transponíveis , Epidermólise Bolhosa Distrófica/genética , Deleção de Sequência , Sequência de Bases , Northern Blotting , Western Blotting , Células Cultivadas , Pré-Escolar , DNA Complementar , Epidermólise Bolhosa Distrófica/patologia , Imunofluorescência , Humanos , Masculino , Microscopia Eletrônica , Dados de Sequência Molecular , Mutação , Linhagem , Polimorfismo Genético , Pele/patologia , Pele/ultraestruturaRESUMO
Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian cancers in a large French pedigree, raising the possibility that a single genetic mutation might cause these conditions and offering a potential lead to the identification of a hereditary breast/ovarian cancer gene. We have performed linkage analysis and show that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected individuals. A single base mutation within the rod domain of the protein cosegregates with EPPK in all affected individuals tested. Although inheritance of this mutation is likely responsible for EPPK, it is unlikely to be the cause of the breast and ovarian cancer.
Assuntos
Neoplasias da Mama/genética , Queratinas/genética , Ceratodermia Palmar e Plantar/genética , Neoplasias Ovarianas/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Neoplasias da Mama/complicações , Cromossomos Humanos Par 17 , Análise Mutacional de DNA , Primers do DNA/genética , Feminino , França , Ligação Genética , Humanos , Ceratodermia Palmar e Plantar/complicações , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasias Ovarianas/complicações , Linhagem , Mutação PuntualRESUMO
BACKGROUND: Efficacy and tolerance should be considered in topical treatments of chronicle affections with impaired skin barrier function such as ichthyosis. OBJECTIVES: To demonstrate the efficacy of Dexeryl in reducing severity of ichthyosis. METHODS: A prospective, multicentre, randomized, placebo controlled study was performed with patients under 18 years suffering from a non-bullous form of ichthyosis. A double-blind period using Dexeryl (an emollient cream containing glycerol 15% and paraffin 10%) or placebo (its vehicle) during 4 weeks followed by an open label period with all patients treated by Dexeryl for 8 weeks. Improvement of ichthyosis was assessed by cutaneous xerosis evolution (SRRC score): the percentage of patients with 50% reduction of the SRRC score at D28 was the primary criterion. The assessment of pruritus [visual analogue scale (VAS)], global evaluation and safety were secondary. RESULTS: The percentage of patients with at least 50% reduction of SRRC score at D28 was significantly higher in Dexeryl group (60.3%) vs. vehicle group (43.5%; P = 0.008). Reduction of pruritus on VAS was significantly higher at D28 with Dexeryl (-2.16) compared to that in placebo (-1.49), P < 0.05. The improvement continues through the open label period: at D84 we observed -2.5 of SRRC score in the Dexeryl group vs.-1.8 for the group previously treated by vehicle. Investigators found Dexeryl efficacy as satisfying for about 80% of treated patients vs. 50% with vehicle. Concerning safety, most of the adverse events were not related to treatment. CONCLUSIONS: Dexeryl showed a significant improvement of xerosis and related symptoms in children with ichthyosis and was well tolerated.
Assuntos
Glicerol/uso terapêutico , Ictiose/tratamento farmacológico , Parafina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients' quality of life (QoL). OBJECTIVES: To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. METHODS: In this 9-month prospective, open-label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3-week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self-assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. RESULTS: The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (-56% vs. baseline; mean ± SD 3·59 ± 4·30 at D18 vs. 8·35 ± 5·71 at D0; P < 0·0001), but also at 3 months (-28% vs. baseline; P = 0·01) and 6 months after hydrotherapy (-26% vs. baseline; mean ± SD 5·21 ± 5·11 vs. 6·89 ± 5·38; P = 0·03) (primary criterion). Clinical symptoms were also significantly improved at all post-treatment visits, with a decrease of the mean clinical ichthyosis score by -38% between D0 and D18, by -30% at 3 months and by -31% at 6 months vs. baseline. CONCLUSIONS: A 3-week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses.
Assuntos
Hidroterapia/métodos , Ictiose/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Ictiose/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Mal de Meleda (MDM, OMIM #248300) is a rare congenital palmoplantar keratosis. Deep fissures cause pain and limit extension of the metacarpo-phalangeal joints. We report the case of a patient operated on both hands with a 29-year interval between each hand. OBSERVATIONS: A 53-year-old patient with MDM demonstrated severe keratosis of the left hand. The same surgeon operated on the right hand. Both hands were operated using the same technique. Skin of the palm, the palmar side of the index, and the first phalangeal of third, fourth and fifth fingers were excised with a sharp rugine. The hand was immediately covered by a full thickness-skin graft (FTSG) harvested on groin. CONCLUSIONS: The excision of all keratosis on the palm can lead to complete cure of MDM symptoms. FTSG is essential, especially on the fingers, in order to minimize secondary retraction. At the palm, FTSG offers better mechanical resistance then a split-thickness skin graft. A large groin graft, with closure of the donor site in a Y fashion, can cover the entire hand. Long term follow-up (29 years) demonstrates no recurrence of keratosis on surgically treated areas.
Assuntos
Ceratodermia Palmar e Plantar/cirurgia , Transplante de Pele/métodos , Virilha/cirurgia , Humanos , Ceratodermia Palmar e Plantar/congênito , Ceratodermia Palmar e Plantar/tratamento farmacológico , Ceratodermia Palmar e Plantar/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Reoperação , Retinoides/uso terapêutico , Transplante de Pele/instrumentação , Síndrome , Transplante Autólogo , Resultado do TratamentoAssuntos
Cromossomos Humanos Par 13 , Conexinas/genética , Displasia Ectodérmica/genética , Mutação de Sentido Incorreto , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Arginina , Mapeamento Cromossômico , Conexina 30 , Feminino , Glicina , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Linhagem , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Previous studies have correlated the Herlitz junctional epidermolysis bullosa (H-JEB) to an altered expression of the basement membrane component nicein/kalinin. This heterotrimeric glycoprotein appears to be present in H-JEB tissues in an abnormal form, because a number of antibodies specific to the protein either do not react with or weakly stain the epidermal basement membranes of most of the patients. With cDNA probes encoding each subunit of nicein and polyclonal antibodies raised against bacterial fusion polypeptides corresponding to the individual chains of the protein, we have molecularly analyzed the expression of nicein in H-JEB tissues and cultured keratinocytes. By immunohistochemistry, Northern blot, and protein analysis, we show a defective synthesis of one of the nicein subunits in six cases of H-JEB from five different consanguineous families. In two patients, the disease correlates with an impaired synthesis of the nicein B2 (nic B2) chain, in three others with that of the B1 (nic B1) chain, and in a sixth patient with that of the heavy A (nic A) chain. In this report, we thus demonstrate that H-JEB is a genetically heterogeneous disease and we provide strong evidence that the genes of nicein are the candidates for this genodermatosis.
Assuntos
Moléculas de Adesão Celular/biossíntese , Epidermólise Bolhosa Juncional/genética , Epidermólise Bolhosa Juncional/metabolismo , Expressão Gênica , Queratinócitos/metabolismo , Pele/metabolismo , Northern Blotting , Moléculas de Adesão Celular/análise , Células Cultivadas , Epidermólise Bolhosa Juncional/patologia , Feto , Imunofluorescência , Humanos , Recém-Nascido , Substâncias Macromoleculares , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Valores de Referência , CalininaRESUMO
Generalized recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited autosomal disease characterized by dermolytic blister formation. Enhanced collagenase and/or abnormal collagenase have been reported in skin from affected patients, suggesting that collagenase could be responsible for the absence of anchoring fibrils in this disorder. We used a genetic linkage approach to test the hypothesis that this disease is due to a defect in the collagenase gene in nine affected families. Analysis of amplified genomic DNA fragments of the collagenase gene by means of denaturing gradient gel electrophoresis (DGGE) allowed us to detect intragenic polymorphisms, which were subsequently characterized by direct genomic sequencing. Segregation analysis of these polymorphic sites showed exclusion of linkage between the collagenase gene and generalized RDEB phenotype in a family with consanguineous parents and three affected children. However, the possibility of linkage with the collagenase gene in the other eight families tested could not be excluded. The genetic markers described here provide a tool for investigating genetic linkage in other affected families. Overall, our results show that generalized RDEB can be caused by a defect in a gene other than the collagenase gene, and support the hypothesis that the genetic defect lies in abnormal anchoring fibril formation.
Assuntos
Epidermólise Bolhosa Distrófica/genética , Ligação Genética , Colagenase Microbiana/genética , Sequência de Bases , Epidermólise Bolhosa Distrófica/enzimologia , Haplótipos , Humanos , Dados de Sequência Molecular , Fenótipo , Polimorfismo GenéticoRESUMO
Generalized mutilating recessive dystrophic epidermolysis bullosa (RDEB) is characterized by extreme skin fragility owing to loss of dermal-epidermal adherence. Immunohistochemical studies have implicated type VII collagen, the major component of anchoring fibrils, in the etiology of RDEB. In this study, we demonstrate genetic linkage of the type VII collagen gene and the generalized mutilating RDEB phenotype. We first identified a Pvull polymorphic site by digestion of an amplified product of the type VII collagen gene, which was shown to reside within the coding region. Genetic linkage analysis between this marker and the RDEB phenotype in 19 affected families which were informative for this polymorphism showed no recombination events, and gave a maximum lod score of 3.97 at a recombination fraction (theta) of 0, demonstrating that this DNA region is involved in this form of RDEB. These data provide strong evidence that the type VII collagen gene, which has also been linked with the dominant form of the disease, harbors the mutation(s) causing the generalized mutilating form of RDEB in these families, thus underscoring the major functional importance of type VII collagen in basement membrane zone stability.
Assuntos
Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Genes Recessivos , Ligação Genética , Sequência de Bases , Mapeamento Cromossômico , Humanos , Dados de Sequência Molecular , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: To evaluate the acceptability, tolerance and efficacy of Urgotul wound dressing in the management of epidermolysis bullosa (EB) skin lesions. METHOD: This was an open-label uncontrolled clinical trial involving 20 patients (I I adults and nine children) with EB simplex or dystrophic EB. Patients were selected from the register of EB patients at the investigating centre and included if they presented with at least one skin lesion requiring management with a non-adherent wound dressing. Lesions were treated with the study dressing for a maximum of four weeks. All dressing changes, wound parameters, pain and effect on quality of life were recorded. RESULTS: All patients completed the trial. Nineteen out of 20 wounds healed within 8.7 +/- 8.5 days. Overall, 11 patients (55%) considered that their quality of life had improved following use of the dressing, which was also reported to be pain free and 'very easy' or 'easy' to remove at most dressing changes. Nineteen out of 20 patients stated that they would use the study dressing to manage their lesions in future. CONCLUSION: This study confirmed the very good acceptability and efficacy of Urgotul in the treatment of skin lesions in patients with EB.
Assuntos
Coloides/uso terapêutico , Epidermólise Bolhosa/terapia , Curativos Oclusivos , Vaselina/uso terapêutico , Adolescente , Adulto , Curativos Hidrocoloides , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Cicatrização/efeitos dos fármacosRESUMO
We have studied 11 patients with the papillomavirus-induced disease epidermodysplasia verruciformis (EV). Clinical diagnostic features are widespread, long-lasting, pityriasis versicolor-like macules and flat, wart-like papules, both usually occurring in early childhood, with the subsequent development in the third decade of multiple skin cancers of the Bowenoid in situ and squamous cell types, primarily in sun-exposed skin. Virologic studies using the methods of immunofluorescence microscopy, restriction endonuclease analysis, and DNA blot hybridization have shown benign lesions to be associated with one or several types of the human papillomaviruses (HPVs) specifically associated with EV (at least 15 types recognized on the basis of sequence homology studies of molecularly cloned genomes). Skin cancers in these patients were associated with the genomes of either HPV-5, HPV-8 or HPV-14, suggesting that these three viruses are potentially oncogenic. A genetic factor appears to play a role in the pathogenesis of EV, since 5 of our patients were children of consanguineous parents and 2 had siblings also suffering with EV, suggesting a recessive inheritance pattern. Treatment of 4 EV patients with an oral retinoid resulted in partial temporary improvement of benign lesions, and the treatment of 2 patients with intralesional interferon injections into multiple Bowenoid cancers in situ has resulted in the disappearance of these lesions. Finally, EV serves as a model for studying the interplay of oncogenic viruses, genetic and immunologic factors, and sunlight in the production of skin cancer in humans.
Assuntos
Nevo/microbiologia , Lesões Pré-Cancerosas/microbiologia , Neoplasias Cutâneas/microbiologia , Infecções Tumorais por Vírus/microbiologia , Adulto , Animais , DNA de Neoplasias/genética , DNA Viral/genética , Avaliação de Medicamentos , Feminino , Imunofluorescência , Humanos , Interferon Tipo I/uso terapêutico , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Nevo/tratamento farmacológico , Nevo/patologia , Hibridização de Ácido Nucleico , Papillomaviridae/genética , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Retinoides/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Síndrome , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/patologiaRESUMO
Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, periodontitis, and premature loss of dentition. Mutations in the CTSC gene that encodes cathepsin C have been described in families affected with Papillon--Lefèvre syndrome. Cathepsin C is the least understood of the lysosomal cysteine proteases; it has been reported to participate in both intracellular and extracellular cleavage of proteins and activation of serine proteases in immune and inflammatory cells. We report here eight new mutations in Papillon-Lefèvre syndrome families: four deletions and four point mutations, including a missense mutation in the propeptide chain that could help elucidate structure-function relationships in this protein. We also found that the 458C > T mutation, first reported in two families by Hart et al (2000c), was a neutral polymorphism in our families, as suggested by Allende et al (Cathepsin C gene: first compound heterozygous patient with Papillon--Lefèvre syndrome and novel symptomless mutation. Hum Mutat 17:152-153, 2001).
Assuntos
Catepsina C/genética , Deleção de Genes , Doença de Papillon-Lefevre/genética , Mutação Puntual , Polimorfismo Genético , África do Norte , Cromossomos Humanos Par 11 , Análise Mutacional de DNA , Europa (Continente) , Saúde da Família , Feminino , Genótipo , Humanos , Masculino , LinhagemRESUMO
Junctional forms of epidermolysis bullosa (JEB) are characterized by tissue separation at the level of the lamina lucida. We have recently disclosed specific mutations in the LAMA3, LAMB3, and LAMC2 genes encoding the subunit polypeptides of the anchoring filament protein laminin 5 in 66 families with different variants of JEB. Examination of the JEB mutation database revealed recurrence of a particular C-->T substitution at nucleotide position 1903 (exon 14) of LAMB3, resulting in the mutation R635X. The inheritance of this nonsense mutation was noted on different genetic backgrounds, suggesting that R635X is a hotspot mutation. In this study, we have performed mutation evaluation in a European cohort of 14 families with the lethal, Herlitz type of JEB (H-JEB). The families were first screened for the presence of the R635X mutation by restriction enzyme digestion of the PCR product corresponding to exon 14. Four of the probands were found to be homozygous and six were heterozygous for R635X. The remaining alleles were subjected to mutation screening by PCR amplification of individual exons of LAMB3 and LAMC2, followed by heteroduplex analysis and nucleotide sequencing. In three families (six alleles), mutations in LAMC2 were disclosed. In the remaining eight alleles, additional pathogenetic LAMB3 mutations were found. None of the patients had LAMA3 mutation. Thus, LAMB3 mutations accounted for 22 of 28 JEB alleles (79%), and a total of 14 of 22 LAMB3 alleles (64%) harbored the R635X mutation, signifying its prevalence as a predominant genetic lesion underlying H-JEB in this European cohort of patients. This recurrent mutation will facilitate screening of additional JEB patients for the purpose of prenatal testing of fetuses at risk for recurrence.
Assuntos
Moléculas de Adesão Celular/genética , Epidermólise Bolhosa Juncional/genética , Mutação , Antígenos/imunologia , Autoantígenos/imunologia , Moléculas de Adesão Celular/imunologia , Análise Mutacional de DNA , Epidermólise Bolhosa Juncional/imunologia , Epitopos/genética , Europa (Continente)/etnologia , Técnica Direta de Fluorescência para Anticorpo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Dados de Sequência Molecular , Estudos Prospectivos , CalininaRESUMO
Linkage analyses in generalized recessive dystrophic epidermolysis bullosa (RDEB) have implicated the type VII collagen gene (COL7A1), which encodes the major component of anchoring fibrils, and recent identification of COL7A1 mutations has provided direct evidence for COL7A1 defects underlying RDEB. In this study, COL7A1 gene analysis was used to successfully perform first-trimester prenatal diagnosis in six families at risk for recurrence of the disease. In four families, three affected with the most severe variant of RDEB (the Hallopeau-Siemens form, HS-RDEB) and one with generalized nonmutilating RDEB, prenatal diagnosis was established by linkage analysis using polymerase chain reaction-based detection of PvuII and AluI intragenic restriction fragment length polymorphism. In two other HS-RDEB families, prenatal diagnosis was carried out by direct detection of mutations in COL7A1, using denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genomic fragments. Analysis of fetal DNA from chorionic villus biopsy or from amniotic fluid cells showed that the fetus had inherited at least one normal COL7A1 allele in all cases. Therefore, the fetus was predicted to be unaffected in the six pregnancies, and this has been confirmed in the newborn infants. Genotype analysis with COL7A1 polymorphic markers, or direct COL7A1 mutation detection in families at risk for the disease, represent early and rapid diagnostic alternatives to second-trimester evaluation of fetal skin samples, and thus offer a major advance in prenatal diagnosis of this life-threatening form of epidermolysis bullosa.
Assuntos
Epidermólise Bolhosa Distrófica/diagnóstico , Diagnóstico Pré-Natal , Sequência de Bases , Colágeno/genética , Epidermólise Bolhosa Distrófica/genética , Feminino , Ligação Genética , Marcadores Genéticos , Genótipo , Humanos , Dados de Sequência Molecular , Mutação , Gravidez , RecidivaRESUMO
Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease which belongs to the palmo-plantar keratoderma (PPK) group. It is characterized by a premature loss of primary and permanent teeth and early onset periodontitis. High consanguinity has been observed in over one-third of PLS families. No candidate genes or gene localizations have been described to date for this disorder. A primary genome-wide search by homozygosity mapping using samples from a large consanguineous family in which 4 siblings were affected by the disease showed homozygosity and linkage in the region of 11q14. Linkage was confirmed in 4 additional families with diverse ethnic and geographic backgrounds, 2 of which were consanguineous. A maximum two-point lod score of 8.19 was obtained for the marker AFM063yg1 (D11S901= for theta = 0. Analysis of recombination events places the gene within a 7-cM interval between AFM063yg1 and AFM269yg9 (D11S4175). No shared haplotype was found for the 5 families analysed.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 11/genética , Doença de Papillon-Lefevre/genética , Consanguinidade , DNA/análise , Feminino , Corantes Fluorescentes , Frequência do Gene , Ligação Genética , Genótipo , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Hibridização de Ácido Nucleico , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Lamellar ichthyosis (LI) is an autosomal recessive genodermatosis which has been shown to be both clinically and genetically heterogeneous. Keratinocyte transglutaminase (or transglutaminase 1: TGM1) has been demonstrated to be the disease-causing gene in some families, whilst in others, a second unidentified LI gene was mapped to chromosome 2q33-35 (ICR2B locus). In this study, we present a physical map that encompasses the ICR2B locus, including the mapping of new microsatellite markers. Based on this new map, genotyping additional families highly suggests a reduction in size of the candidate interval. The final interval is covered by a single yeast artificial chromosome (937-H-3) which is 2.2Mb in length. Fine mapping of potential candidate transcripts was also focused on this region.
Assuntos
Cromossomos Humanos Par 2 , Ictiose Lamelar/genética , Mapeamento Físico do Cromossomo , Cromossomos Artificiais de Levedura , Feminino , Fibronectinas/genética , Humanos , Masculino , LinhagemRESUMO
We report 3 cases of bullous immunoglobulinic amyloidosis and review 25 published cases. In 2 of our patients, amyloid deposits were not detected with special staining, but by means of ultrastructural methods. Investigations of the skin lesions permitted the diagnosis of associated plasma cell dyscrasia in 2 patients. Unexplained bullous lesions should be investigated for amyloid deposits and the presence of monoclonal gammopathy by methods including electron microscopy and immunochemical analysis of serum and urine.
Assuntos
Amiloidose/diagnóstico , Paraproteinemias/diagnóstico , Dermatopatias Vesiculobolhosas/diagnóstico , Idoso , Amiloidose/complicações , Amiloidose/imunologia , Amiloidose/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Paraproteinemias/complicações , Paraproteinemias/imunologia , Paraproteinemias/metabolismo , Dermatopatias Vesiculobolhosas/etiologia , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/metabolismoRESUMO
Neurofibromatosis type 1 (NF1), a genetic disorder with neuroectodermal involvement, demonstrates phenotypic overlap in some patients with Noonan syndrome (NS), ultimately resulting in the so-called neurofibromatosis-Noonan syndrome (NF-NS). A strong association of the two phenotypic traits was recently illustrated by a four-generation family, although NF1 and NS were eventually demonstrated to segregate independently on the basis of polymorphic DNA markers [Bahuau et al., 1996: Am J Med Genet 66:347-355]. Identification of the causal NF1 mutation seemed a prerequisite to further dissecting this singular familial association. Using the protein truncation assay, a nonsense mutation (C2446T-->R816X) of the neurofibromin gene was evidenced. This mutation occurred on a CpG dinucleotide within exon 16 and 5' to the GAP domain-specifying region of the gene. R816X creates a recognition site for endonuclease HphI, absent in 2 individuals with NS only. Screening 184 unrelated NF1 patients, three novel occurrences of the mutation were found in individuals diagnosed with classical NF1. Based on the assumption of genotype-phenotype correlation in these individuals, clinical and molecular analyses of this four-generation family demonstrated that the NF-NS phenotype was additive, being the result of both classical NF1 and NS. This particular observation also suggests the presence of an NS locus on 17q, which might be of interest for further linkage studies.