title: Unequal crossover recombination - population screening for PHOX2B gene polyalanine polymorphism using CE.
abstract: Congenital central hypoventilation syndrome (CCHS) is a rare neurological disorder characterized by abnormal autonomic central nervous system control of breathing during sleep. Mutations in the paired-like homeobox 2B (PHOX2B) gene, including point mutation, frameshift, and polyalanine expansion, are associated with the pathogenesis of CCHS. In this study, PHOX2B mutations were analyzed in seven CCHS patients, their family members, and 1520 healthy individuals from the general population using CE to provide high sensitivity and resolution screening for the PHOX2B polyalanine polymorphism. Seven mutations in the PHOX2B gene, including two frameshift mutations and five polyalanine expansions in the 20-residue polyalanine tract, were identified. The various phenotypes observed in CCHS patients with PHOX2B mutations suggest that the size of the expansion allele is associated with the CCHS risk. In addition, significant differences were found in allele and genotype distributions between the healthy individuals. Alleles (GCN)(20) and (GCN)(15) had the highest population incidence rates of 94.84 and 4.51%, respectively, with the remaining alleles, (GCN)(13) and (GCN)(7), accounting for 0.59 and 0.06%, respectively. Therefore, it has been demonstrated that CE can be used to improve the detection of polyalanine expansions in the PHOX2B gene. The attractive alternative method is a promising tool for the detection of disorders involving trinucleotide repeat tracts.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Hung
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.forename: Pau-Chung
authors.initials: PC
authors.lastname: Chen
authors.forename: Shio-Jean
authors.initials: SJ
authors.lastname: Lin
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Mu
authors.forename: Chieh-An
authors.initials: CA
authors.lastname: Liu
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chang
authors.forename: Win-Li
authors.initials: WL
authors.lastname: Lin
authors.forename: Wu-Shiun
authors.initials: WS
authors.lastname: Hsieh
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
mesh_terms: D000328:Adult; D002675:Child, Preschool; D003434:Crossing Over, Genetic; D019075:Electrophoresis, Capillary; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007040:Hypoventilation / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine