Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome

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 pro...

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Bibliographic Details
Published in:	Archives of medical research Vol. 47; no. 2; pp. 105 - 110
Main Authors:	Kallabi, Fakhri, Belghuith, Neila, Aloulou, Hajer, Kammoun, Thouraya, Ghorbel, Soufiane, Hajji, Mouna, Gallas, Syrine, Chemli, Jaleleddine, Chabchoub, Imen, Azzouz, Hatem, Ben Chehida, Amel, Sfaihi, Lamia, Makni, Saloua, Amouri, Ali, Keskes, Leila, Tebib, Neji, Ben Becher, Saayda, Hachicha, Monjia, Kamoun, Hassen
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-02-2016
Subjects:	AAAS gene Achalasia Adrenal insufficiency Adrenal Insufficiency - genetics Adrenal Insufficiency - physiopathology Alacrima Allgrove syndrome Amplified Fragment Length Polymorphism Analysis Child Child, Preschool Esophageal Achalasia - genetics Esophageal Achalasia - physiopathology Female Homozygote Humans Infant Internal Medicine Major mutation Male Mutation Nerve Tissue Proteins - genetics Nuclear Pore Complex Proteins - genetics Tunisia Allgrove syndrome Achalasia Adrenal insufficiency Alacrima AAAS gene Major mutation
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0188-4409 1873-5487
DOI:	10.1016/j.arcmed.2016.04.004