RESUMO
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
The medical records of 306 British soldiers in whom a clinical diagnosis of cutaneous leishmaniasis had been made following a tour of duty in Belize were analysed. Parasitological confirmation of the diagnosis was established in 187 cases; leishmania were cultured in 117 cases and Leishman-Donovan bodies were identified histologically in a further 70 cases. Leishmania braziliensis braziliensis was identified in 78 cases and Leishmania mexicana mexicana in a further 29 cases. Seventy-one per cent of patients had a single lesion which, in most cases, occurred on the exposed extremities. The mean diameter of the ulcers was 14.4 mm. Treatment with sodium stibogluconate was effective. Two regimens were used, consisting of either 600-800 mg daily given initially for 10 days, or 600 mg b.d. given initially for 14 days. Of those allocated to the lower dose regimen 48.5% were cured after the initial 10-day course, and ultimately the ulcers of 93% of patients healed following more prolonged treatment at this dose. Of those allocated to the higher dose regimen 63.9% were cured after the initial 14-day course and ultimately the ulcers of all patients healed after more prolonged treatment at this dose. A transient leucopenia and a rise in liver enzymes were noted during treatment, and these changes were dose-dependent. No cases of mucocutaneous leishmaniasis were encountered.
Assuntos
Leishmania braziliensis , Leishmania mexicana , Leishmaniose Cutânea/parasitologia , Militares , Adulto , Animais , Gluconato de Antimônio e Sódio/uso terapêutico , Belize/epidemiologia , Esquema de Medicação , Seguimentos , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Masculino , Reino Unido/etnologiaRESUMO
The medical records of 306 British soldiers in whom a clinical diagnosis of cutaneous leishmaniasis had been made following a tour of duty in Belize were analysed. Parasitological confirmation of the diagnosis was established in 187 cases; leishmania were cultured in 117 cases and leishman-Donovan bodies were identified in 78 cases and Leishmania mexicana mexicana in a further 29 cases. Leishmania braziliensis was indentified in 78 cases and Leishmania mexicana mexicana in a further 29 cases. Seventy-one per cent of patients had a single lesion which, in most cases, occurred on the exposed extremities. The mean diameter of the ulcers was 14.4 mm. Treatment with sodium stobogluconate was effective. Two regimens were used, consisting of either 600-800 mg daily given initially for 10 days, or 600 mg b.d. given initially for 14 days. Of those allocated to the lower dose regimen 48.5 percent were cured after the initial 10-day course, and ultimately the ulcers of 93 percent of patients healed following more prolonged treatment at this dose. Of those allocated to the higher dose regiment 63.9 percent were cured after the initial 14-day course and ultimately the ulcers of all patients healed after more prolonged treatement at this dose. A transient leucopenia and a rise in liver enzymes were noted during treatment, and these changes were dose-dependent. No cases of mucocutaneous leishmaniasis were encountered (AU)