title: Clinical and molecular investigation of Buschke-Fischer-Brauer in consanguineous Tunisian families.
abstract: 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.
  
  
  CONCLUSIONS
  This study contributes to further characterize PPPK-BFB in consanguineous families and to extend the mutational spectrum of AAGAB gene in the Tunisian population.
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.|High Institut of Biotechnology of Sidi Thabet, University of Manouba, Biotechpole of SidiThabet, Ariana, Tunisia.
authors.forename: C
authors.initials: C
authors.lastname: Charfeddine
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: C
authors.initials: C
authors.lastname: Ktaifi
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: N
authors.initials: N
authors.lastname: Laroussi
authors.affiliation: Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia.|Laboratory of Genodermatosis and Cancer (LR12SP03), University of Tunis El Manar, Faculty of Medecine Tunis, Tunis, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Hammami
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Jmel
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: Z
authors.initials: Z
authors.lastname: Landoulsi
authors.affiliation: Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia.
authors.forename: T
authors.initials: T
authors.lastname: Badri
authors.affiliation: Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia.
authors.forename: R
authors.initials: R
authors.lastname: Benmously
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Bchetnia
authors.affiliation: Department of Human and Experimental Pathology, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: M S
authors.initials: MS
authors.lastname: Boubaker
authors.affiliation: Department of Dermatology, Habib Thameur Hospital, Tunis, Tunisia.|Laboratory of Genodermatosis and Cancer (LR12SP03), University of Tunis El Manar, Faculty of Medecine Tunis, Tunis, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: Fenniche
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics (LR11IPT05), University of Tunis El Manar, Pasteur Institut of Tunis, Tunis, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Department of Dermatology, CHU La Rabta Tunis, Tunis, Tunisia.|CHU La Rabta Tunis, Research Unit on Hereditary Keratinizaton Disorders UR12SP07, Tunis, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Mokni
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D003241:Consanguinity; D005260:Female; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014416:Tunisia; D055815:Young Adult