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WNT10B mutations in human obesity

WNT10B mutations in human obesity
WNT10B mutations in human obesity

Aims/hypothesis: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene.

Subjects and methods: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin.

Results: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties.

Conclusions/ interpretation: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

Adipocyte, Adipogenesis, Human, Obesity, WNT
0012-186X
678-684
Christodoulides, C.
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Scarda, A.
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Granzotto, M.
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Milan, G.
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Dalla Nora, E.
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Keogh, J.
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De Pergola, G.
ab66517c-38a2-4c66-a106-1a47749ec07d
Stirling, H.
e61042d5-6525-4e98-a55e-5ce734c35a91
Pannacciulli, N.
37947b0d-c30d-4bb1-b9ea-b685ec5e0b62
Sethi, J.K.
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Federspil, G.
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Vidal-Puig, A.
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Farooqi, I.S.
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O'Rahilly, S.
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Vettor, R.
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Christodoulides, C.
ea12b5f7-a2a9-44bf-86a5-59fcfb0a320a
Scarda, A.
f054a6ed-e1b1-44b9-b10e-116331ae2b58
Granzotto, M.
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Milan, G.
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Dalla Nora, E.
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Keogh, J.
a6f2eec9-69cd-4164-9c1f-bedf77812f34
De Pergola, G.
ab66517c-38a2-4c66-a106-1a47749ec07d
Stirling, H.
e61042d5-6525-4e98-a55e-5ce734c35a91
Pannacciulli, N.
37947b0d-c30d-4bb1-b9ea-b685ec5e0b62
Sethi, J.K.
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Federspil, G.
e32ebd0a-16c8-4d82-ba9a-8e190984b3cf
Vidal-Puig, A.
e63d69a6-77fe-4c3d-821f-75e3aba1919b
Farooqi, I.S.
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O'Rahilly, S.
4dbefabf-bb9d-4784-9a0a-54f8e413a7bb
Vettor, R.
038128e3-d2ae-4496-8277-d50b244c15de

Christodoulides, C., Scarda, A., Granzotto, M., Milan, G., Dalla Nora, E., Keogh, J., De Pergola, G., Stirling, H., Pannacciulli, N., Sethi, J.K., Federspil, G., Vidal-Puig, A., Farooqi, I.S., O'Rahilly, S. and Vettor, R. (2006) WNT10B mutations in human obesity. Diabetologia, 49 (4), 678-684. (doi:10.1007/s00125-006-0144-4).

Record type: Article

Abstract

Aims/hypothesis: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene.

Subjects and methods: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin.

Results: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties.

Conclusions/ interpretation: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

Full text not available from this repository.

More information

e-pub ahead of print date: 14 February 2006
Published date: April 2006
Keywords: Adipocyte, Adipogenesis, Human, Obesity, WNT

Identifiers

Local EPrints ID: 415412
URI: https://eprints.soton.ac.uk/id/eprint/415412
ISSN: 0012-186X
PURE UUID: e8fcb8df-3f34-422c-8411-5e5f24021997
ORCID for J.K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

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Date deposited: 09 Nov 2017 17:30
Last modified: 29 Aug 2019 00:26

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Contributors

Author: C. Christodoulides
Author: A. Scarda
Author: M. Granzotto
Author: G. Milan
Author: E. Dalla Nora
Author: J. Keogh
Author: G. De Pergola
Author: H. Stirling
Author: N. Pannacciulli
Author: J.K. Sethi ORCID iD
Author: G. Federspil
Author: A. Vidal-Puig
Author: I.S. Farooqi
Author: S. O'Rahilly
Author: R. Vettor

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