De novo t(12;17)(p13.3;q21.3) translocation with a breakpoint near the 5' end of the HOXB gene cluster in a patient with developmental delay and skeletal malformations.
A boy with severe mental retardation, funnel chest, bell-shaped thorax, and hexadactyly of both feet was found to have a balanced de novo t(12;17)(p13.3;q21.3) translocation. FISH with BAC clones and long-range PCR products assessed in the human genome sequence localized the breakpoint on chromosome 17q21.3 to a 21-kb segment that lies <30 kb upstream of the HOXB gene cluster and immediately adjacent to the 3' end of the TTLL6 gene. The breakpoint on chromosome 12 occurred within telomeric hexamer repeats and, therefore, is not likely to affect gene function directly. We propose that juxtaposition of the HOXB cluster to a repetitive DNA domain and/or separation from required cis-regulatory elements gave rise to a position effect.
Yue
Ying
Y
Institute for Human Genetics, Johannes Gutenberg University Mainz, Mainz, Germany.
Farcas
Ruxandra
R
Thiel
Gundula
G
Bommer
Christiane
C
Grossmann
Bärbel
B
Galetzka
Danuta
D
Kelbova
Christina
C
Küpferling
Peter
P
Daser
Angelika
A
Zechner
Ulrich
U
Haaf
Thomas
T
D002675:Child, Preschool; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000235:genetics*; D014178:Translocation, Genetic