Clinical and molecular investigation of Buschke-Fischer-Brauer in consanguineous Tunisian families.

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.

Hailey-Hailey disease in Tunisia.

SUMMARY BACKGROUND: Most of the published reports on Hailey-Hailey disease (HHD) come from European and Asian countries. We report here the clinical and genetic investigation of 20 patients affected with HHD in Tunisia. METHODS: Affected individuals from three large teaching hospitals in Tunis were recruited for the study over a 25-year period. Nine patients were identified through the active files and examined together with their family members that were visited in their respective regions. We have clinically examined in total 65 individuals and then identified 11 new cases. Patients were included on the basis of evocative skin lesions, biopsy proven HHD and negative immunofluorescence. Investigations to rule out fungal, bacterial and viral infections were done according to clinical symptoms. RESULTS: Twenty patients (12 males and 8 females) from 8 families were included in the present study with more than 55% that were undiagnosed before this investigation. Four patients had mild disease, eight had moderate disease and another eight had severe disease, among whom seven were females. Parental consanguinity was found in 7 cases out of 20 cases (35%). The neck region was first affected in half (4/8) of the male patients. Groins were first affected in 42% (5/12) of the female patients. Depression complicated the course of the disease in two female patients with severe HHD. We report an original association of supernumerary nipples with HHD in two sisters from the north of Tunisia. In 10 patients, the disease has become less troublesome with aging. CONCLUSION: HHD is underestimated. Physicians must be aware of this disease in case of resistant intertriginous dermatosis especially with a positive family history as nine out of 20 patients were misdiagnosed.

Histological characterization of Darier's disease in Tunisian families.

BACKGROUND: Darier's disease (OMIM 124200) is an autosomal-dominant skin disorder characterized by warty papules and plaques in seborreheic areas, palmo-plantar pits and distinctive nail abnormalities. The disease has complete penetrance in adults and variable expressivity. It is caused by mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase type 2 isoform (SERCA2). OBJECTIVE: We report histological investigations of six unrelated Tunisian families including 15 affected individuals with Darier's disease mutations. RESULTS: The typical histological features of Darier's disease have been observed in the 15 patients. Variable histological features have been observed among Tunisian patients ranging from mild to moderate lesions of Darier's disease. A significant correlation has been observed between the clinical presentation of the Darier's disease (mild or moderate) and the intensity of the histological features. Isolated acral form of Darier's disease was seen in one case. Two distinct original associations have been observed: Darier's disease/pemphigus vulgaris in one patient and Darier's disease/ichtyosis in the other patient. CONCLUSION: Our findings confirmed the clinical heterogeneity of Darier's disease on the basis of histological study. The intensity of the histological features could be closely correlated to the severity of Darier's disease clinical presentation.

Supernumerary nipples in association with Hailey-Hailey disease in a Tunisian family.

Supernumerary nipples (SNs) or polythelia are developmental abnormalities of breast tissue. They are located along the embryonic mammary lines. Polythelia usually occurs as a sporadic abnormality, although familial aggregation has been occasionally reported. Hailey-Hailey disease is a rare autosomal genodermatosis characterized by disturbed keratinocyte adhesion. These cutaneous disorders have been described in correlation with many other abnormalities. We report here the association of Hailey-Hailey disease and supernumerary nipples in a Northern Tunisian family. To our knowledge, this is the first report of such a clinical association.