Idiopathic congenital central hypoventilation syndrome: Evaluation of brain‐derived neurotrophic factor genomic DNA sequence variation
- 10 January 2002
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics
- Vol. 107 (4), 306-310
- https://doi.org/10.1002/ajmg.10133
Abstract
Idiopathic congenital central hypoventilation syndrome (CCHS) is an unique disorder of respiratory control, occurring in association with Hirschsprung disease (HSCR), tumors of neural crest origin, and symptoms of autonomic nervous system dysfunction (ANSD). CCHS is thought to be genetic in origin based upon 1) affected sib pairs, 2) genetic analysis, and 3) identification of genetic mutations in both HSCR and CCHS patients. Because these mutations have been found in but a few cases of CCHS, exploration of other candidate genes has continued. Brain‐derived neurotrophic factor (BDNF) represents a potential candidate gene to consider because of altered respiratory control in the BDNF knock‐out mouse model and localization to the enteric nervous system in human tissue. The objective of this study was to determine the frequency of BDNF mutations among 19 children with CCHS (five with HSCR) compared to 40 unaffected unrelated controls. Using the known genomic DNA sequence for BDNF, polymerase chain reaction (PCR)‐amplified genomic DNA was analyzed by standard sequencing methods. A discrete mutation was identified in one of 19 children with isolated CCHS and the unaffected father. Specifically, an isoleucine was substituted for a threonine or serine in the amino acid sequence. Absence of this mutation in 40 controls confirmed that this mutation was likely not a common polymorphism. These data further support a genetic basis for CCHS, though mutations of BDNF are not consistent in this disorder.Keywords
This publication has 50 references indexed in Scilit:
- Cardiac rhythm disturbances among children with idiopathic congenital central hypoventilation syndromePediatric Pulmonology, 2000
- Cardio-respiratory control in an infant with Ondine's curse: a multivariate autoregressive modelling approachJournal of the Autonomic Nervous System, 1993
- Ondine-Hirschsprung syndrome (Haddad syndrome)European Journal of Pediatrics, 1993
- Congenital central hypoventilation syndrome: Diagnosis, management, and long-term outcome in thirty-two childrenThe Journal of Pediatrics, 1992
- Hirschsprung's disease and Ondine's curse: further evidence for a distinct syndromeClinical Genetics, 1989
- Congenital central hypoventilation syndrome in monozygotic twinsThe Journal of Pediatrics, 1988
- Ondine's Curse and NeurocristopathyClinical Pediatrics, 1980
- Control of ventilation in Ondine's curseThe Journal of Pediatrics, 1980
- TOTAL AGANGLIONOSIS OF THE COLON AND ONDINE'S CURSEThe Lancet, 1980
- Congenital failure of automatic ventilation (Ondine's curse): A case reportThe Journal of Pediatrics, 1974