Document Detail


Mutation of HOXA13 in hand-foot-genital syndrome.
MedLine Citation:
PMID:  9020844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There are several human syndromes which involve defects of the limbs and the Müllerian ducts or its derivatives. The hand-foot-genital (HFG) syndrome is an autosomal dominant, fully penetrant disorder that was originally described by Stern et al. Additional reports describing other affected families have also been published. Limb anomalies include short first metacarpals of normal thickness, small distal phalanges of the thumbs, short middle phalanges of the fifth fingers, and fusion or delayed ossification of wrist bones. In the feet, the great toe is shorter due to a short first metatarsal and a small, pointed distal phalanx. Uterine anomalies are common in females with HFG, and typically involve a partially divided (bicornuate) or completely divided (didelphic) uterus, representing defects of Müllerian duct fusion. Urinary tract malformations in affected HFG females include a displaced urethral opening and malposition of ureteral orifices in the bladder wall; affected males may have hypospadias (ventrally misplaced urethral opening) of variable severity. We report the identification of a HOXA13 nonsense mutation in a family with hand-foot-genital syndrome. The mutation converts a highly conserved tryptophan residue in the homeodomain to a stop codon, which truncates 20 amino acids from the protein and likely eliminates or greatly reduces the ability of the protein to bind to DNA.
Authors:
D P Mortlock; J W Innis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature genetics     Volume:  15     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-03-10     Completed Date:  1997-03-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  179-80     Citation Subset:  IM    
Affiliation:
Dept of Human Genetics, Univ of Michigan Medical School, Ann Arbor 48109-0618, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/U82827
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / genetics*
Amino Acid Sequence
Codon / genetics
DNA / metabolism
DNA Mutational Analysis
Female
Foot Deformities, Congenital / genetics*
Hand Deformities, Congenital / genetics*
Homeodomain Proteins / chemistry,  genetics*,  metabolism
Humans
Hypospadias / genetics*
Male
Molecular Sequence Data
Pedigree
Point Mutation*
Protein Binding
Protein Structure, Tertiary
Structure-Activity Relationship
Syndrome
Urethra / abnormalities*
Uterus / abnormalities*
Grant Support
ID/Acronym/Agency:
5 P60 AR20557/AR/NIAMS NIH HHS; HD34059/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Codon; 0/Homeodomain Proteins; 0/homeobox protein HOXA13; 9007-49-2/DNA
Comments/Corrections
Comment In:
Nat Genet. 1997 Feb;15(2):117-8   [PMID:  9020831 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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