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PMID: 15106123 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutations in the human TBX4 gene cause small patella syndrome.

American journal of human genetics ·Vol. 74 ·No. 6 ·2004-06-00 ·Pages 1239-48

Bongers EM, Duijf PH, van Beersum SE, Schoots J, Van Kampen A, Burckhardt A, Hamel BC, Losan F, Hoefsloot LH, Yntema HG, Knoers NV, van Bokhoven H

Abstract

Small patella syndrome (SPS) is an autosomal-dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. We identified an SPS critical region of 5.6 cM on chromosome 17q22 by haplotype analysis. Putative loss-of-function mutations were found in a positional gene encoding T-box protein 4 (TBX4) in six families with SPS. TBX4 encodes a transcription factor with a strongly conserved DNA-binding T-box domain that is known to play a crucial role in lower limb development in chickens and mice. The present identification of heterozygous TBX4 mutations in SPS patients, together with the similar skeletal phenotype of animals lacking Tbx4, establish the importance of TBX4 in the developmental pathways of the lower limbs and the pelvis in humans.

MeSH Terms
Adolescent Adult Amino Acid Sequence Bone Diseases, Developmental/genetics Chromosomes, Human, Pair 17/genetics Female Haplotypes/genetics Heterozygote Humans Male Molecular Sequence Data Mutation/genetics Patella/abnormalities Pedigree Pelvic Bones/abnormalities Protein Conformation Protein Folding Sequence Homology, Amino Acid Syndrome T-Box Domain Proteins/deficiency,genetics
Chemicals
T-Box Domain Proteins TBX4 protein, human
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Bongers Ernie M H F
Department of Human Genetics, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands.
Duijf Pascal H G
van Beersum Sylvia E M
Schoots Jeroen
Van Kampen Albert
Burckhardt Andreas
Hamel Ben C J
Losan Frantisek
Hoefsloot Lies H
Yntema Helger G
Knoers Nine V A M
van Bokhoven Hans
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/421331
Published
2004-06-00
Epub
2004-00-21
Pages
1239-48
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1182087
Subset
IM
Databases
GENBANK
AF188703, U28049
External Links
PubMed source DOI: 10.1086/421331 PMC Full Text View journal details
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