PHOX2B mutations in patients with Ondine–Hirschsprung disease and a review of the literature
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Min-Jung Kwon & Gi-Hyuck Lee & Myoung-Keun Lee & Ji-Youn Kim & Hye Soo Yoo & Chang-Seok Ki & Yun Sil Chang & Jong-Won Kim &Won Soon Park
- چاپ و سال / کشور: 2011
Description
Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine– Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR
Eur J Pediatr DOI 10.1007/s00431-011-1434-5 Received: 15 November 2010 / Accepted: 11 February 2011
