A candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocation

Hum Genet. 2002 Mar;110(3):244-50. doi: 10.1007/s00439-002-0679-5. Epub 2002 Feb 1.


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.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Blepharoptosis / congenital*
  • Blepharoptosis / genetics*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • DNA / genetics
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Species Specificity
  • Transcription Factors / genetics*
  • Translocation, Genetic*
  • Zinc Fingers / genetics


  • Homeodomain Proteins
  • Transcription Factors
  • Zfhx4 protein, mouse
  • DNA