Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome
Open accessAbstract
Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.
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Tbx3 is the T-box gene that is mutated in human ulnar-mammary syndrome.
“Here we show that Tbx3, the T-box gene that is mutated in human ulnar-mammary syndrome, is specifically expressed in multipotent hepatic progenitor cells, 'hepatoblasts', isolated from the developing mouse liver.”
From Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing <i>p19ARF</i> expression (2008) · cites this paper as Bamshad et al., 1997
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“TBX3 is the germline genetic variant associated with the ulnar-mammary syndrome, a rare pleiotropic disorder with an autosomal dominant inheritance pattern and incomplete penetrance affecting upper limb development and ulnar and mammary apocrine sweat glands [17].”
- Authors
- Bamshad, M., Lin, R. C., Law, D. J., Watkins, W. S., Krakowiak, P. A., Moore, M. E., Franceschini, P., Lala, R., Holmes, L. B., Gebuhr, T. C., Bruneau, B. G., Schinzel, A., Seidman, J. G., Seidman, C. E., & Jorde, L. B.
- Affiliations
- University of Utah (US)
- Howard Hughes Medical Institute (US)
- University of Michigan (US)
- University of Turin (IT)
- Ospedale Regina Margherita (IT)
- Massachusetts General Hospital (US)
- University of Zurich (CH)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Nature Genetics
- Published
- 1997-07-01
- Volume
- 16
- Issue
- 3
- Pages
- 311-315
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2018892038
- Cited by
- 540
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 14 · 2015: 14 · 2014: 22 · 2013: 30 · 2012: 23
- FWCI
- 18.12
- Type
- journal article
- Language
- en
- Update notices
- correction (1998-05-01)
- Open access
- green
- doi.org
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health (5p30hg000199-03)
- U.S. Public Health Service (M01-00064)
- National Human Genome Research Institute (5P30 HG00199, HG-00209)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- ulnar-mammary syndrome, TBX3, TBX5, T-box transcription factor, haploinsufficiency, limb development, genital development, tooth development, Holt-Oram syndrome, gene evolution
- MeSH terms
- Abnormalities, Multiple, Amino Acid Sequence, Apocrine Glands, Arm, Base Sequence, Breast, Chromosomes, Human, Pair 12, DNA Mutational Analysis, Female, Genitalia, Humans, Introns, Male, Molecular Sequence Data, Mutation, Syndrome, Transcription Factors, Sequence Alignment, Gene Expression Regulation, Developmental, T-Box Domain Proteins
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