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Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q

Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q
Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q


Context: Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ resistance to PTH and other hormones such as TSH in the absence of any features of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting abnormalities at the complex GNAS locus. The molecular cause of autosomal dominant familial PHP1b has been well-defined with identification of microdeletions within the GNAS locus or the nearby STX16, but the molecular mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive.

Objective: We investigated the underlying molecular mechanism of GNAS imprinting defects in two patients with sporadic PHP1b.

Results: We identified paternal uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated patients with sporadic PHP1b. This provides an explanation for the patients' GNAS methylation abnormalities and hormone resistance. Our data and a review of the six published cases of patUPD20 suggest that high birth weight and/or early-onset obesity and macrocephaly may also represent features of patUPD20.

Conclusion: We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.
0021-972X
E103-E108
Dixit, A.
d6b2cef3-ba34-4e51-bd3f-1fa5db51982d
Chandler, K.E.
07b24f9f-8f21-49eb-abb6-85a1d71a4dfe
Lever, M.
4e322ec3-7007-4b49-9ba1-6006e4167146
Poole, R.L.
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Bullman, H.
75ccf2b2-5a55-4b89-be72-19b43683aaf8
Mughal, M.Z.
4858093f-9bb9-4521-87cd-d7463770d8c7
Steggall, M.
9e58b700-0609-4a4e-b6c2-a080855d0cc8
Suri, M.
d524dd38-f856-450f-8ab5-2611011f2bdf
Dixit, A.
d6b2cef3-ba34-4e51-bd3f-1fa5db51982d
Chandler, K.E.
07b24f9f-8f21-49eb-abb6-85a1d71a4dfe
Lever, M.
4e322ec3-7007-4b49-9ba1-6006e4167146
Poole, R.L.
d8fe00fa-9deb-4a34-a7d8-4b7f57ce82fa
Bullman, H.
75ccf2b2-5a55-4b89-be72-19b43683aaf8
Mughal, M.Z.
4858093f-9bb9-4521-87cd-d7463770d8c7
Steggall, M.
9e58b700-0609-4a4e-b6c2-a080855d0cc8
Suri, M.
d524dd38-f856-450f-8ab5-2611011f2bdf

Dixit, A., Chandler, K.E., Lever, M., Poole, R.L., Bullman, H., Mughal, M.Z., Steggall, M. and Suri, M. (2013) Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q. Journal of Clinical Endocrinology & Metabolism, 98 (1), E103-E108. (doi:10.1210/jc.2012-2639). (PMID:23144470)

Record type: Article

Abstract



Context: Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ resistance to PTH and other hormones such as TSH in the absence of any features of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting abnormalities at the complex GNAS locus. The molecular cause of autosomal dominant familial PHP1b has been well-defined with identification of microdeletions within the GNAS locus or the nearby STX16, but the molecular mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive.

Objective: We investigated the underlying molecular mechanism of GNAS imprinting defects in two patients with sporadic PHP1b.

Results: We identified paternal uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated patients with sporadic PHP1b. This provides an explanation for the patients' GNAS methylation abnormalities and hormone resistance. Our data and a review of the six published cases of patUPD20 suggest that high birth weight and/or early-onset obesity and macrocephaly may also represent features of patUPD20.

Conclusion: We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.

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More information

e-pub ahead of print date: 8 November 2012
Published date: January 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 345248
URI: http://eprints.soton.ac.uk/id/eprint/345248
ISSN: 0021-972X
PURE UUID: 0710f144-8add-453b-9dbe-39f390bb1808

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Date deposited: 11 Jan 2013 11:55
Last modified: 22 Jul 2022 18:16

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Contributors

Author: A. Dixit
Author: K.E. Chandler
Author: M. Lever
Author: R.L. Poole
Author: H. Bullman
Author: M.Z. Mughal
Author: M. Steggall
Author: M. Suri

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