Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13.
Hox genes regulate patterning during limb development. It is believed that they function in the determination of the timing and extent of local growth rates. Here, it is demonstrated that synpolydactyly, an inherited human abnormality of the hands and feet, is caused by expansions of a polyalanine stretch in the amino-terminal region of HOXD13. The homozygous phenotype includes the transformation of metacarpal and metatarsal bones to short carpal- and tarsal-like bones. The mutations identify the polyalanine stretch outside of the DNA binding domain of HOXD13 as a region necessary for proper protein function.
Muragaki
Y
Y
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Mundlos
S
S
Upton
J
J
Olsen
B R
BR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000196:embryology; D005801:Genes, Homeobox; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D010455:Peptides / Q000737:chemistry; D017689:Polydactyly / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011859:Radiography; D013576:Syndactyly / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics*; D014034:Toes / Q000002:abnormalities* / Q000196:embryology; D014157:Transcription Factors
C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine