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

• Published in: Human genetics Vol. 110; no. 3; pp. 244 - 250
• Main Authors: MCMULLAN, Tristan F. W, CROLLA, John A, GREGORY, Simon G, CARTER, Nigel P, COOPER, Rachel A, HOWELL, Gareth R, ROBINSON, David O
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-03-2002; Berlin Springer Nature B.V; New York, NY
• Subjects: Adult; Animals; Base Sequence; Biological and medical sciences; Blepharoptosis - congenital; Blepharoptosis - genetics; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 8 - genetics; Classical genetics, quantitative genetics, hybrids; Diseases of eyelid, conjunctiva and lacrimal tracts; DNA - genetics; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Homeodomain Proteins - genetics; Human; Humans; In Situ Hybridization, Fluorescence; Male; Medical sciences; Mice; Molecular Sequence Data; Ophthalmology; Polymerase Chain Reaction; Species Specificity; Transcription Factors - genetics; Translocation, Genetic; Zinc Fingers - genetics; Chromosomal aberration; Genetic mapping; Human; Nucleotide sequence; Zinc finger structure; Ptosis; Homology; Case study; Eye disease; Chromosome break; Eyelid disease; Homeotic gene; Abnormal chromosome; Candidate gene; Physical map; Chromosome translocation
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-002-0679-5

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.