title: Genome-wide linkage analysis and mutation analysis of hereditary congenital blepharoptosis in a Japanese family.
abstract: Hereditary congenital ptosis (PTOS) is defined as drooping of the upper eyelid without any other accompanying symptoms and distinguished from syndromic blepharoptosis. Two previous linkage analyses assigned a PTOS locus (PTOS1) to 1p32-p34.1 and another (PTOS2) to Xq24-q27.1. In addition, in a sporadic case with a balanced chromosomal translocation t(1;8) (p34.3;q21.12), the ZFHX4 (zinc finger homeodomain 4) gene was found to be disrupted at the 8q21.12 breakpoint, but there was no gene at the 1p34.3 breakpoint, suggesting the existence of the third PTOS locus (PTOS1) at 8q21.12. We carried out a genome-wide linkage analysis in a Japanese PTOS family and calculated two-point and multipoint log of odds (LOD) scores with reduced penetrance. Haplotype analysis gave three candidate disease-responsible regions, i.e., 8q21.11-q22.1, 12q24.32-q24.33, and 14q21.1-q23.2. Although the family size is too small to define one of them, 8q21.11-q22.1 is a likely candidate region, because it contains the previously reported translocation breakpoint above. We thus performed mutation, Southern-blot and methylation analyses of ZFHX4 but could not find any disease-specific change in the family. Nevertheless, our data may support the localization of PTOS1.
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.|Division of Plastic and Reconstructive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Division of Plastic and Reconstructive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Division of Plastic and Reconstructive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.|Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
authors.affiliation: Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.|Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondoh
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.|Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Miwa
authors.affiliation: The Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.|Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan. kyoshi@nagasaki-u.ac.jp.|Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Tokyo, Japan. kyoshi@nagasaki-u.ac.jp.
authors.forename: Koh-Ichiro
authors.initials: KI
authors.lastname: Yoshiura
mesh_terms: D001763:Blepharoptosis / Q000151:congenital* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D010375:Pedigree; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics