Fakhri Kallabi1, Neila Belghuith2, Hajer Aloulou3, Thouraya Kammoun3, Soufiane Ghorbel4, Mouna Hajji5, Syrine Gallas6, Jaleleddine Chemli7, Imen Chabchoub3, Hatem Azzouz8, Amel Ben Chehida8, Lamia Sfaihi3, Saloua Makni5, Ali Amouri9, Leila Keskes10, Neji Tebib8, Saayda Ben Becher5, Monjia Hachicha3, Hassen Kamoun11. 1. Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia. Electronic address: fakhrikallabi@yahoo.fr. 2. Department of Medical Genetics, C.H.U. Hedi Chaker, Sfax, Tunisia. 3. Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia. 4. Department of Pediatric Surgery B, Children's Hospital Bechir Hamza, Tunis, Tunisia. 5. Department of Pediatrics, Children's Hospital Bechir Hamza, Tunis, Tunisia. 6. Physiology Laboratory, Faculty of Medicine, Monastir, Tunisia. 7. Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia. 8. Department of Pediatrics, La Rabta Hospital, Tunis, Tunisia. 9. Department of Gastroenterology, C.H.U. Hedi Chaker, Sfax, Tunisia. 10. Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia. 11. Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia; Department of Pediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.