title: Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome.
abstract: Allgrove syndrome is characterized by achalasia, alacrima, and adrenal insufficiency as well as being associated with progressive neurological signs. This is an autosomal recessive disorder due to mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes a protein of 546 amino acids, ALADIN. Mutations in this genwere reported in families from North Africa and Europe. Our objective is to conduct a clinical, molecular and genetic study of 26 Tunisian patients with Allgrove syndrome.
  
  
  
  We report 26 Tunisian patients with between two and four clinical features associated with Allgrove syndrome. Blood samples were collected and isolated DNA derived from subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR and sequencing. PCR-RFLP method was performed to identify the frequent mutations found.
  
  
  
  Sequencing of the AAAS gene revealed a major homozygous mutation (c.1331+1G>A) in 25 patients and R286X mutation in one patient. The presence of a major mutation in several unrelated affected individuals suggests the presence of a founder effect in Tunisia and allows for a fast and targeted molecular diagnosis.
  
  
  
  We created an easy and rapid molecular enzymatic protocol based on PCR-RFLP using MvaI restriction enzyme that directly targets this major mutation and can be used for prenatal diagnosis and genetic counseling for Tunisian families at risk. To the best of our knowledge, this is the first major series report of Allgrove syndrome in Tunisia.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia. Electronic address: fakhrikallabi@yahoo.fr.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Kallabi
authors.affiliation: Department of Medical Genetics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Neila
authors.initials: N
authors.lastname: Belghuith
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Hajer
authors.initials: H
authors.lastname: Aloulou
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Thouraya
authors.initials: T
authors.lastname: Kammoun
authors.affiliation: Department of Pediatric Surgery B, Children's Hospital Bechir Hamza, Tunis, Tunisia.
authors.forename: Soufiane
authors.initials: S
authors.lastname: Ghorbel
authors.affiliation: Department of Pediatrics, Children's Hospital Bechir Hamza, Tunis, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Hajji
authors.affiliation: Physiology Laboratory, Faculty of Medicine, Monastir, Tunisia.
authors.forename: Syrine
authors.initials: S
authors.lastname: Gallas
authors.affiliation: Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia.
authors.forename: Jaleleddine
authors.initials: J
authors.lastname: Chemli
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Chabchoub
authors.affiliation: Department of Pediatrics, La Rabta Hospital, Tunis, Tunisia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Azzouz
authors.affiliation: Department of Pediatrics, La Rabta Hospital, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Ben Chehida
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Sfaihi
authors.affiliation: Department of Pediatrics, Children's Hospital Bechir Hamza, Tunis, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Makni
authors.affiliation: Department of Gastroenterology, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Amouri
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: Department of Pediatrics, La Rabta Hospital, Tunis, Tunisia.
authors.forename: Neji
authors.initials: N
authors.lastname: Tebib
authors.affiliation: Department of Pediatrics, Children's Hospital Bechir Hamza, Tunis, Tunisia.
authors.forename: Saayda
authors.initials: S
authors.lastname: Ben Becher
authors.affiliation: Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Monjia
authors.initials: M
authors.lastname: Hachicha
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia; Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Hassen
authors.initials: H
authors.lastname: Kamoun
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics* / Q000503:physiopathology*; D054458:Amplified Fragment Length Polymorphism Analysis; D002648:Child; D002675:Child, Preschool; D004931:Esophageal Achalasia / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D014416:Tunisia
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins
keywords: AAAS gene; Achalasia; Adrenal insufficiency; Alacrima; Allgrove syndrome; Major mutation