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Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
Background

Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.

Methods

We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons.

Results

We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1×10?7). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies.
autism, methods, abnormalities, classification, microcephaly, diagnosis, expression, congenital, disease, genome, phenotype, anomalies, genotype, mental retardation, human, patients, technology, cataract, deletions, children
1685-1699
Mefford, H.C.
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Sharp, A.J.
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Baker, C.
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Itsara, A.
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Jiang, Z.
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Buysse, K.
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Huang, S.
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Maloney, V.K.
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Crolla, J.A.
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Baralle, D.
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Collins, A.
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Mercer, C.
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Norga, K.
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De Ravel, T.
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Devriendt, K.
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De Leeuw, N.
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Reardon, W.
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Simonic, I.
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Mehta, S.G.
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Tolmie, J.L.
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Lilley, C.
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Armengol, L.
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Verloo, P.
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De Coene, A.
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Goossens, L.
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Mortier, G.
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Speleman, F.
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Skinner, C.
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Stevenson, R.E.
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Antonarakis, S.E.
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Chen, C.
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Estivill, X.
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Menten, B.
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Gimelli, G.
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Gribble, S.
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Schwartz, S.
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Sutcliffe, J.S.
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Walsh, T.
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Romano, C.
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Schwartz, C.E.
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Veltman, J.A.
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De Vries, B.B.
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Vermeesch, J.R.
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Barber, J.C.
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Willatt, L.
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Tassabehji, M.
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Eichler, E.E.
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Mefford, H.C.
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Sharp, A.J.
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Baker, C.
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Itsara, A.
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Jiang, Z.
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Buysse, K.
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Huang, S.
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Maloney, V.K.
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Crolla, J.A.
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Baralle, D.
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Collins, A.
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Mercer, C.
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Norga, K.
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De Ravel, T.
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Devriendt, K.
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Bongers, E.M.
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De Leeuw, N.
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Reardon, W.
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Gimelli, S.
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Bena, F.
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Hennekam, R.C.
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Male, A.
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Gaunt, L.
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Simonic, I.
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Park, S.M.
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Mehta, S.G.
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Nik-Zainal, S.
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Woods, C.G.
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Firth, H.V.
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Parkin, G.
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Fichera, M.
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Reitano, S.
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Giudice, M.L.
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Li, K.E.
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Casuga, I.
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Broomer, A.
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Conrad, B.
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Schwerzmann, M.
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Raber, L.
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Gallati, S.
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Striano, P.
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Coppola, A.
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Tolmie, J.L.
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Mortier, G.
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Speleman, F.
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Van Binsbergen, E.
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Nelen, M.R.
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Hochstenbach, R.
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Regan, R.
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Stevenson, R.E.
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Antonarakis, S.E.
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Chen, C.
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Estivill, X.
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Menten, B.
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Gimelli, G.
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Gribble, S.
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Schwartz, S.
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Walsh, T.
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Knight, S.J.
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Romano, C.
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Veltman, J.A.
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De Vries, B.B.
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Vermeesch, J.R.
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Barber, J.C.
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Willatt, L.
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Tassabehji, M.
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Eichler, E.E.
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Mefford, H.C., Sharp, A.J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., Huang, S., Maloney, V.K., Crolla, J.A., Baralle, D., Collins, A., Mercer, C., Norga, K., De Ravel, T., Devriendt, K., Bongers, E.M., De Leeuw, N., Reardon, W., Gimelli, S., Bena, F., Hennekam, R.C., Male, A., Gaunt, L., Clayton-Smith, J., Simonic, I., Park, S.M., Mehta, S.G., Nik-Zainal, S., Woods, C.G., Firth, H.V., Parkin, G., Fichera, M., Reitano, S., Giudice, M.L., Li, K.E., Casuga, I., Broomer, A., Conrad, B., Schwerzmann, M., Raber, L., Gallati, S., Striano, P., Coppola, A., Tolmie, J.L., Tobias, E.S., Lilley, C., Armengol, L., Spysschaert, Y., Verloo, P., De Coene, A., Goossens, L., Mortier, G., Speleman, F., Van Binsbergen, E., Nelen, M.R., Hochstenbach, R., Poot, M., Gallagher, L., Gill, M., McClellan, J., King, M.C., Regan, R., Skinner, C., Stevenson, R.E., Antonarakis, S.E., Chen, C., Estivill, X., Menten, B., Gimelli, G., Gribble, S., Schwartz, S., Sutcliffe, J.S., Walsh, T., Knight, S.J., Sebat, J., Romano, C., Schwartz, C.E., Veltman, J.A., De Vries, B.B., Vermeesch, J.R., Barber, J.C., Willatt, L., Tassabehji, M. and Eichler, E.E. (2008) Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. New England Journal of Medicine, 359 (16), 1685-1699. (doi:10.1056/NEJMoa0805384). (PMID:18784092)

Record type: Article

Abstract

Background

Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.

Methods

We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons.

Results

We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1×10?7). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies.

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More information

Published date: September 2008
Keywords: autism, methods, abnormalities, classification, microcephaly, diagnosis, expression, congenital, disease, genome, phenotype, anomalies, genotype, mental retardation, human, patients, technology, cataract, deletions, children
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Identifiers

Local EPrints ID: 70777
URI: http://eprints.soton.ac.uk/id/eprint/70777
DOI: doi:10.1056/NEJMoa0805384
PURE UUID: 80344be4-6beb-403e-bb94-146fa753ee3d
ORCID for D. Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 06 Jan 2010
Last modified: 14 Mar 2024 02:53

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Contributors

Author: H.C. Mefford
Author: A.J. Sharp
Author: C. Baker
Author: A. Itsara
Author: Z. Jiang
Author: K. Buysse
Author: S. Huang
Author: V.K. Maloney
Author: J.A. Crolla
Author: D. Baralle ORCID iD
Author: A. Collins
Author: C. Mercer
Author: K. Norga
Author: T. De Ravel
Author: K. Devriendt
Author: E.M. Bongers
Author: N. De Leeuw
Author: W. Reardon
Author: S. Gimelli
Author: F. Bena
Author: R.C. Hennekam
Author: A. Male
Author: L. Gaunt
Author: J. Clayton-Smith
Author: I. Simonic
Author: S.M. Park
Author: S.G. Mehta
Author: S. Nik-Zainal
Author: C.G. Woods
Author: H.V. Firth
Author: G. Parkin
Author: M. Fichera
Author: S. Reitano
Author: M.L. Giudice
Author: K.E. Li
Author: I. Casuga
Author: A. Broomer
Author: B. Conrad
Author: M. Schwerzmann
Author: L. Raber
Author: S. Gallati
Author: P. Striano
Author: A. Coppola
Author: J.L. Tolmie
Author: E.S. Tobias
Author: C. Lilley
Author: L. Armengol
Author: Y. Spysschaert
Author: P. Verloo
Author: A. De Coene
Author: L. Goossens
Author: G. Mortier
Author: F. Speleman
Author: E. Van Binsbergen
Author: M.R. Nelen
Author: R. Hochstenbach
Author: M. Poot
Author: L. Gallagher
Author: M. Gill
Author: J. McClellan
Author: M.C. King
Author: R. Regan
Author: C. Skinner
Author: R.E. Stevenson
Author: S.E. Antonarakis
Author: C. Chen
Author: X. Estivill
Author: B. Menten
Author: G. Gimelli
Author: S. Gribble
Author: S. Schwartz
Author: J.S. Sutcliffe
Author: T. Walsh
Author: S.J. Knight
Author: J. Sebat
Author: C. Romano
Author: C.E. Schwartz
Author: J.A. Veltman
Author: B.B. De Vries
Author: J.R. Vermeesch
Author: J.C. Barber
Author: L. Willatt
Author: M. Tassabehji
Author: E.E. Eichler

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