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- Title
De novo polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: unequal sister chromatid exchange during paternal gametogenesis.
- Authors
Arai, Hiroko; Otagiri, Tesshu; Sasaki, Ayako; Hashimoto, Taeko; Umetsu, Kazuo; Tokunaga, Katsushi; Hayasaka, Kiyoshi
- Abstract
The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHOX2B in 13 de novo families with CCHS and found that 6 families were informative regarding a parental origin of polyalanine expansion, with all 6 mutants being of paternal origin. Four of them were also informative regarding a chromosomal event and their mutants were derived from unequal sister chromatid exchange. It is probable that de novo expansion of polyalanine repeats in CCHS results mainly from unequal sister chromatid exchange during spermatogenesis due to the secondary DNA structure of imperfect trinucleotide repeats encoding polyalanine tracts.
- Subjects
HYPERVENTILATION syndrome; SISTER chromatid exchange; CHROMOSOME replication; GAMETOGENESIS; CELL differentiation; HUMAN genetics
- Publication
Journal of Human Genetics, 2007, Vol 52, Issue 11, p921
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1007/s10038-007-0197-3