title: Molecular Analysis of Libyan Families with Allgrove Syndrome: Geographic Expansion of the Ancestral Mutation c.1331+1G>A in North Africa.
abstract: OBJECTIVE
  Allgrove syndrome is a rare autosomal recessive disorder characterized by alacrima, achalasia, and adrenal insufficiency. It is caused by mutations of the AAAS gene located on chromosome 12q13 encoding the WD-repeat protein ALADIN. The c.1331+1G>A mutation is one of the most common mutations described in the literature and was identified in Tunisian and Algerian populations. Herein, we describe the clinical and genetic profile of two families from Libya in North Africa associated with Allgrove syndrome.
  
  
  METHODS
  Two unrelated families clinically diagnosed with Allgrove syndrome were evaluated for sequence variations in the AAAS gene. Blood samples were collected, and isolated DNA derived from the subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR-RFLP and direct sequencing.
  
  
  RESULTS
  Molecular analysis revealed the major homozygous mutation (c.1331+1G>A) in all patients. The presence of a major mutation in Tunisia, Algeria and, as discovered in this report, in Libya in patients with Allgrove syndrome suggests the existence of an ancestral mutation and a founder effect in North Africa.
  
  
  CONCLUSIONS
  The findings allow for a fast genetic counseling in North African families with Allgrove syndrome. To the best of our knowledge, this is the first report of Allgrove syndrome in Libya.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Kallabi
authors.forename: Imen
authors.initials: I
authors.lastname: Ben Rebeh
authors.forename: Rahma
authors.initials: R
authors.lastname: Felhi
authors.forename: Dorra
authors.initials: D
authors.lastname: Sellami
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.forename: Hassen
authors.initials: H
authors.lastname: Kamoun
mesh_terms: D000309:Adrenal Insufficiency / Q000453:epidemiology* / Q000235:genetics*; D004931:Esophageal Achalasia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006720:Homozygote; D006801:Humans; D008002:Libya / Q000453:epidemiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D017354:Point Mutation
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins