A HOXA13 Allele with a Missense Mutation in the Homeobox and a Dinucleotide Deletion in the Promoter Underlies Guttmacher Syndrome

Author(s)

Jeffrey W. Innis, University of Michigan-Ann Arbor
Frances R. Goodman, University of London - Institute of Child Health
Chiara Bacchelli, University of London - Institute of Child Health
Thomas M. Williams, University of DaytonFollow
Douglas Mortlock, University of Michigan-Ann Arbor
Praveen Sateesh, University of Michigan-Ann Arbor
Peter J. Scambler, University of London - Institute of Child Health
Wendy McKinnon, Vermont Regional Genetics Center
Alan E. Guttmacher, National Institutes of Health

Document Type

Article

Publication Date

4-2002

Publication Source

Human Mutation

Abstract

Guttmacher syndrome, a dominantly inherited combination of distal limb and genital tract abnormalities, has several features in common with hand-foot-genital syndrome (HFGS), including hypoplastic first digits and hypospadias. The presence of features not seen in HFGS, however, including postaxial polydactyly of the hands and uniphalangeal 2nd toes with absent nails, suggests that it represents a distinct entity. HFGS is caused by mutations in the HOXA13 gene. We have therefore re-investigated the original Guttmacher syndrome family, and have found that affected individuals are heterozygous for a novel missense mutation in the HOXA13 homeobox (c.1112A>T; homeodomain residue Q50L), which arose on an allele already carrying a novel 2-bp deletion (-78-79delGC) in the gene’s highly conserved promoter region. This deletion produces no detectable abnormalities on its own, but may contribute to the phenotype in the affected individuals. The missense mutation, which alters a key residue in the recognition helix of the homeodomain, is likely to perturb HOXA13’s DNA-binding properties, resulting in both a loss and a specific gain of function.

Inclusive pages

573–574

ISBN/ISSN

1059-7794

Comments

Permission documentation is on file.

Copyright

Copyright © 2002, Wiley-Liss

Publisher

Wiley-Liss

Volume

19

Peer Reviewed

yes

Issue

5

eCommons Citation

Innis, Jeffrey W.; Goodman, Frances R.; Bacchelli, Chiara; Williams, Thomas M.; Mortlock, Douglas; Sateesh, Praveen; Scambler, Peter J.; McKinnon, Wendy; and Guttmacher, Alan E., "A HOXA13 Allele with a Missense Mutation in the Homeobox and a Dinucleotide Deletion in the Promoter Underlies Guttmacher Syndrome" (2002). Biology Faculty Publications. 169.
https://ecommons.udayton.edu/bio_fac_pub/169