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Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences

Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences
Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences
Segmental aneuploidy usually has phenotypic consequences but unbalanced rearrangements without phenotypic consequences have also been reported. In particular, harmless deletions of G-dark bands 5p14 and 16q21 have each been found in more than one independent family. Here, we report two families that were ascertained at prenatal diagnosis and had similar overlapping deletions that removed most of the gene poor G-dark band 2p12. PCR mapping showed that the deletions had a minimum size of 6.1 and 6.9 Mb with at least 13 hemizygous loci including a cluster of six pancreatic islet-regenerating genes. These deletions had no apparent phenotypic consequences in eight family members. In contrast, a third family was ascertained through a child with Wilm's tumour; both the child and his mother had more proximal deletions, developmental delay and some dysmorphic features. The deletion had a minimum size of 5.7 Mb and extended into the gene-rich area of 2p11.2. These results are consistent with the idea that there may be segments of the genome that are consistently haplosufficient. The introduction of higher resolution methods of dosage analysis into diagnostic laboratories is already revealing more transmitted abnormalities of uncertain significance. As a result, published cases of transmitted imbalances have been collected as a guide to the possible significance of such findings in the future (see the 'Chromosome Anomaly Collection' at www.som.soton.ac.uk/research/geneticsdiv).
1018-4813
283-291
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Thomas, N.S.
df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4
Collinson, M.N.
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Dennis, N.R.
154aa617-52e2-4711-98ef-89fef8610de7
Liehr, T.
d07890dd-7be8-42cf-ade9-93a9ab4b5b74
Weise, A.
861da819-f837-48af-b447-02dc6f17edea
Belitz, B.
4340a94d-370f-4d68-92a6-7e6d408532f6
Pfeiffer, L.
9833f5c9-9bd4-4b5b-a970-d1cde534d6a4
Kirchhoff, M.
178e2e5b-8ce4-493d-8031-14ae53ab1a23
Krag-Olsen, B.
4f894192-f7c1-40c3-b1a1-bdc6477efc0e
Lundsteen, C.
e74b7d69-687c-4318-9c56-62146c9332fa
Barber, J.C.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Thomas, N.S.
df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4
Collinson, M.N.
f038514b-d366-4ef6-a480-a9d656e3fdf9
Dennis, N.R.
154aa617-52e2-4711-98ef-89fef8610de7
Liehr, T.
d07890dd-7be8-42cf-ade9-93a9ab4b5b74
Weise, A.
861da819-f837-48af-b447-02dc6f17edea
Belitz, B.
4340a94d-370f-4d68-92a6-7e6d408532f6
Pfeiffer, L.
9833f5c9-9bd4-4b5b-a970-d1cde534d6a4
Kirchhoff, M.
178e2e5b-8ce4-493d-8031-14ae53ab1a23
Krag-Olsen, B.
4f894192-f7c1-40c3-b1a1-bdc6477efc0e
Lundsteen, C.
e74b7d69-687c-4318-9c56-62146c9332fa

Barber, J.C., Thomas, N.S., Collinson, M.N., Dennis, N.R., Liehr, T., Weise, A., Belitz, B., Pfeiffer, L., Kirchhoff, M., Krag-Olsen, B. and Lundsteen, C. (2005) Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences. European Journal of Human Genetics, 13 (3), 283-291. (doi:10.1038/sj.ejhg.5201267).

Record type: Article

Abstract

Segmental aneuploidy usually has phenotypic consequences but unbalanced rearrangements without phenotypic consequences have also been reported. In particular, harmless deletions of G-dark bands 5p14 and 16q21 have each been found in more than one independent family. Here, we report two families that were ascertained at prenatal diagnosis and had similar overlapping deletions that removed most of the gene poor G-dark band 2p12. PCR mapping showed that the deletions had a minimum size of 6.1 and 6.9 Mb with at least 13 hemizygous loci including a cluster of six pancreatic islet-regenerating genes. These deletions had no apparent phenotypic consequences in eight family members. In contrast, a third family was ascertained through a child with Wilm's tumour; both the child and his mother had more proximal deletions, developmental delay and some dysmorphic features. The deletion had a minimum size of 5.7 Mb and extended into the gene-rich area of 2p11.2. These results are consistent with the idea that there may be segments of the genome that are consistently haplosufficient. The introduction of higher resolution methods of dosage analysis into diagnostic laboratories is already revealing more transmitted abnormalities of uncertain significance. As a result, published cases of transmitted imbalances have been collected as a guide to the possible significance of such findings in the future (see the 'Chromosome Anomaly Collection' at www.som.soton.ac.uk/research/geneticsdiv).

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Published date: March 2005

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Local EPrints ID: 24620
URI: https://eprints.soton.ac.uk/id/eprint/24620
ISSN: 1018-4813
PURE UUID: deefe930-9725-4f91-9ccd-8d534508af14

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Date deposited: 03 Apr 2006
Last modified: 26 Feb 2019 17:31

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Contributors

Author: J.C. Barber
Author: N.S. Thomas
Author: M.N. Collinson
Author: N.R. Dennis
Author: T. Liehr
Author: A. Weise
Author: B. Belitz
Author: L. Pfeiffer
Author: M. Kirchhoff
Author: B. Krag-Olsen
Author: C. Lundsteen

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