A t(2;8) balanced translocation with breakpoints near the human HOXD complex causes mesomelic dysplasia and vertebral defects.
Mesomelic dysplasia is a severe shortening of forearms and forelegs, and is found in several distinct human syndromes. Here, we report the cloning of the breakpoints of a human t(2;8)(q31;p21) balanced translocation associated with mesomelic dysplasia of the upper limbs, as well as with vertebral defects. We show that this translocation does not disrupt any gene, hence it most likely exerts its deleterious effect by modifying gene regulation. The HOXD complex lies approximately 60 kb from the translocation breakpoint on chromosome 2. This cluster of genes has an important role in the development of both the vertebral column and the limbs. Only a few cases of mutations of these homeotic genes have been described so far in humans. However, gain- and loss-of-function of Hoxd genes in mice can induce mesomelic dysplasia-like phenotypes, suggesting that misexpression of HOXD genes may indeed be at the origin of this hereditary phenotype.
Spitz
François
F
Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Montavon
Thomas
T
Monso-Hinard
Christine
C
Morris
Michael
M
Ventruto
Maria-Luisa
ML
Antonarakis
Stylianos
S
Ventruto
Valerio
V
Duboule
Denis
D
D001132:Arm / Q000002:abnormalities; D051792:Basic Helix-Loop-Helix Proteins; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007866:Leg / Q000002:abnormalities; D008297:Male; D017422:Sequence Analysis, DNA; D013131:Spine / Q000002:abnormalities*; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489922:Ebf2 protein, mouse; C409450:mxtx2 protein, zebrafish