Format

Send to

Choose Destination
Am J Hum Genet. 2012 Jul 13;91(1):171-9. doi: 10.1016/j.ajhg.2012.05.018. Epub 2012 Jul 5.

HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice.

Author information

1
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.

Abstract

Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of mice and humans. We have identified a founder homozygous missense mutation in HOXB1 in two families from a conservative German American population. The resulting phenotype includes bilateral facial palsy, hearing loss, and strabismus and correlates extensively with the previously reported Hoxb1(-/-) mouse phenotype. The missense variant is predicted to result in the substitution of a cysteine for an arginine at amino acid residue 207 (Arg207Cys), which corresponds to the highly conserved Arg5 of the homeodomain. Arg5 interacts with thymine in the minor groove of DNA through hydrogen bonding and electrostatic attraction. Molecular modeling and an in vitro DNA-protein binding assay predict that the mutation would disrupt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activity.

PMID:
22770981
PMCID:
PMC3397264
DOI:
10.1016/j.ajhg.2012.05.018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center