RESUMEN
BACKGROUND: Punctate palmoplantar keratoderma type I (PPPK-BFB), also called Buschke-Fischer-Brauer disease (MIM 148600) is a rare autosomal dominant disorder of keratinization, characterized by multiple hyperkeratotic lesions on the palms and soles. Recently, PPPK-BFB has been shown to be associated with mutations in the AAGAB gene in several families of European, African, Canadian and Asian origins. OBJECTIVE: To characterize the clinical and genetic features of PPPK-BFB in a broad group of Tunisian patients. METHODS: Epidemiological and clinical data were collected from 18 PPPK-BFB patients belonging to eight Tunisian families. We carried out mutational and structural analysis for families not previously investigated. RESULTS: Sequencing of the remaining families identified a total of three different mutations in AAGAB gene: one founder mutation (c.348_349delAG, p.R116Sfs*1) specific to the inbred Tunisian population, one recurrent mutation and (c.370C>T, p.R124*) one novel variant (c.430C>G, p.E144K). This novel mutation, involving a conserved amino acid, is predicted to be probably damaging to the p34 protein function. Assessment of the phenotypic presentation of this group of Tunisian patients was marked by variable severity and varying age at onset with a possible presence of anticipation noted in five out of eight families (62.5%). There is no apparent genotype-phenotype correlation. Despite the high degree of inbreeding, no homozygous individuals for AAGAB mutations were observed. Homozygous carriers in AAGAB gene are likely non-viable. CONCLUSION: This study contributes to further characterize PPPK-BFB in consanguineous families and to extend the mutational spectrum of AAGAB gene in the Tunisian population.
Asunto(s)
Queratodermia Palmoplantar/patología , Adolescente , Anciano , Anciano de 80 o más Años , Consanguinidad , Femenino , Humanos , Queratodermia Palmoplantar/genética , Masculino , Persona de Mediana Edad , Túnez , Adulto JovenAsunto(s)
Xerodermia Pigmentosa/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/genética , Neoplasias/mortalidad , Linaje , Túnez/epidemiología , Xerodermia Pigmentosa/mortalidad , Adulto JovenRESUMEN
Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.
Asunto(s)
Mutación/genética , Proteína de la Xerodermia Pigmentosa del Grupo A/metabolismo , Xerodermia Pigmentosa/genética , Niño , Preescolar , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Linaje , Fenotipo , Polimorfismo Genético , Túnez , Xerodermia Pigmentosa/fisiopatología , Proteína de la Xerodermia Pigmentosa del Grupo A/genéticaRESUMEN
INTRODUCTION: Pemphigoid gestationis is a bullous autoimmune sub-epidermal dermatosis, occurring during pregnancy and/or postpartum. The objective of our study was to define the epidemio-clinical profile, the histopathological and immunopathological features, the treatment and the course of pemphigoid gestationis in Tunisian patients. PATIENTS AND METHODS: This was a retrospective study concerning the cases of pemphigoid gestationis recorded between 1989 and 2003 in the dermatology department in La Rabta Hospital in Tunis. The patients were included according to clinical, histopathological and immunopathological criteria. RESULTS: We retained 20 patients: 15 multiparae and 5 primiparae. The average age at onset was 29. The first clinical signs appeared in the 3rd trimester in 60 p. 100 of all cases. Clinically, the urticarial patches were noticed in 90 p. 100 of all cases and blisters in 65 p. 100 of the cases. The eruption was located mainly on the trunk and the limbs. The face was affected in 7 cases, the mucous membranes in 3 cases, the palms in 2 cases and the soles in 1 case. Cutaneous histologic examination revealed a sub-epidermal blister in 11 cases and a lymphohistiocyte infiltrate in all cases. Direct immunofluorescence showed a linear deposition of the third component of the complement along the basement membrane zone in all cases. Fetal prognosis was assessed in 13 cases: 1 fetal death, 1 still-born, 3 miscarriages, 1 anencephaly and 2 cases of transit bullous affection in the new-born. DISCUSSION: Our results are similar to those in the literature, but with some particular aspects: the late onset of the pemphigoid gestationis in the course of the 3rd trimester of pregnancy, the frequent involvement of the face and the mucous membranes and the absence of the two main fetal risks: prematurity and hypotrophy. Moreover, we underline the efficiency of topical class I corticosteroids in the treatment of pemphigoid gestationis.