Clinical and genetic characterisation of a series of patients with triple A syndrome

Kurnaz E., Duminuco P., AYCAN Z., Savas-Erdeve S., Sahin N. M., Keskin M., ...Daha Fazla

EUROPEAN JOURNAL OF PEDIATRICS, cilt.177, sa.3, ss.363-369, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 177 Sayı: 3
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1007/s00431-017-3068-8
  • Dergi Adı: EUROPEAN JOURNAL OF PEDIATRICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.363-369
  • Anahtar Kelimeler: Triple A syndrome, ACTH resistance, Adrenal insufficiency, AAAS gene, WD-REPEAT PROTEIN, A SYNDROME, ADRENAL INSUFFICIENCY, ALLGROVE SYNDROME, ACHALASIA, DEFICIENCY, ALACRIMA, AAAS
  • Ankara Üniversitesi Adresli: Hayır

Özet

Triple A syndrome (TAS) or Allgrove syndrome (OMIM #231550) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima, achalasia, and neurological and dermatological abnormalities. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Between 2006 and 2017, we evaluated six patients with a clinical diagnosis of TAS, based on the presence of at least two symptoms, usually adrenal insufficiency and alacrima. In all cases, genetic analysis revealed homozygous mutations in the AAAS gene. One novel mutation was detected: a homozygous 10-bp deletion (c.1264_1273del, p.Q422NfsX126) in exon 14 of the AAAS gene that caused a frameshift that introduced an aberrant stop codon after 126 amino acids. This genetic variant is likely to be pathogenic because it caused a significant change in protein structure. A precise genotype-phenotype correlation was impossible to establish.