title: A candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocation.
abstract: Ptosis is defined as drooping of the upper eyelid and can impair full visual acuity. It occurs in a number of forms including congenital bilateral isolated ptosis, which may be familial and for which two linkage groups are known on chromosomes 1p32-34.1 and Xq24-27.1. We describe the analysis of the chromosome breakpoints in a patient with congenital bilateral isolated ptosis and a de novo balanced translocation 46,XY,t(1;8)(p34.3;q21.12). Both breakpoints were localized by fluorescence in situ hybridisation with yeast artificial chromosomes, bacterial artificial chromosomes and P1 artificial chromosomes. The derived chromosomes were isolated by flow-sorting, amplified by degenerate oligonucleotide-primed polymerase chain reaction and analyzed by sequence tagged sites amplification to map the breakpoints at a resolution that enabled molecular characterization by DNA sequencing. The 1p breakpoint lies ~13 Mb distal to the previously reported linkage locus at 1p32-1p34.1 and does not disrupt a coding sequence, whereas the chromosome 8 breakpoint disrupts a gene homologous to the mouse zfh-4gene. Murine zfh-4 codes for a zinc finger homeodomain protein and is a transcription factor expressed in both muscle and nerve tissue. Human ZFH-4 is therefore a candidate gene for congenital bilateral isolated ptosis.
authors.affiliation: Southampton University School of Medicine, Human Genetics Division, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Tristan W
authors.initials: TW
authors.lastname: McMullan
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Cooper
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.forename: David O
authors.initials: DO
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D001763:Blepharoptosis / Q000151:congenital* / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004247:DNA / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C093452:Zfhx4 protein, mouse; D004247:DNA