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16p11.2–p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2

16p11.2–p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2
16p11.2–p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2
Chromosome 16 contains multiple copy number variations (CNVs) that predispose to genomic disorders. Here, we differentiate pathogenic duplications of 16p11.2–p12.2 from microscopically similar euchromatic variants of 16p11.2. Patient 1 was a girl of 18 with autism, moderate intellectual disability, behavioural difficulties, dysmorphic features and a 7.71-Mb (megabase pair) duplication (16:21?521?005–29?233?146). Patient 2 had a 7.81-Mb duplication (16:21?382?561–29?191?527), speech delay and obsessional behaviour as a boy and, as an adult, short stature, macrocephaly and mild dysmorphism. The duplications contain 65 coding genes of which Polo-like kinase 1 (PLK1) has the highest likelihood of being haploinsufficient and, by implication, a triplosensitive gene. An additional 1.11-Mb CNV of 10q11.21 in Patient 1 was a possible modifier containing the G-protein-regulated inducer of neurite growth 2 (GPRIN2) gene. In contrast, the euchromatic variants in Patients 3 and 4 were amplifications from a 945-kb region containing non-functional immunoglobulin heavy chain (IGHV), hect domain pseudogene (HERC2P4) and TP53-inducible target gene 3 (TP53TG3) loci in proximal 16p11.2 (16:31?953?353–32?898?635). Paralogous pyrosequencing gave a total copy number of 3–8 in controls and 8 to >10 in Patients 3 and 4. The 16p11.2–p12.2 duplication syndrome is a recurrent genomic disorder with a variable phenotype including developmental delay, dysmorphic features, mild to severe intellectual disability, autism, obsessive or stereotyped behaviour, short stature and anomalies of the hands and fingers. It is important to differentiate pathogenic 16p11.2–p12.2 duplications from harmless, microscopically similar euchromatic variants of proximal 16p11.2, especially at prenatal diagnosis
1018-4813
182-189
Barber, John C.K.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Hall, Victoria
33a08845-ce3a-4967-82f8-d3b49ddfcd87
Maloney, Viv K.
a2d7cd03-153c-418a-855d-cf4a8d4e9a50
Huang, Shuwen
44f28908-02b8-46d7-822c-e6a9e7981723
Roberts, Angharad M.
ff1e5c2c-db47-4224-9cbc-4dce0e57db43
Brady, Angela F.
6a592734-d3ec-40dd-a159-f157cd8f56eb
Foulds, Nicki
5e153e9f-caae-45f5-b6f0-943bd567558e
Bewes, Beverley
3d53eb7b-8ea1-423a-87fc-1394b4c79379
Volleth, Marianne
4093d3ae-8b56-4da9-9334-bae514c73389
Liehr, Thomas
b99d17d3-69ab-4bac-8774-5d21177abcda
Mehnert, Karl
52207df7-d1f7-42d4-9972-5709eaacf8db
Bateman, Mark
1fdbeb26-4d05-4ba7-80ce-f16680ddcad9
White, Helen
d5aff204-b128-46c8-8aab-c9be75a97e70
Barber, John C.K.
4785a6e4-bd63-4230-ab61-41a0ae12c761
Hall, Victoria
33a08845-ce3a-4967-82f8-d3b49ddfcd87
Maloney, Viv K.
a2d7cd03-153c-418a-855d-cf4a8d4e9a50
Huang, Shuwen
44f28908-02b8-46d7-822c-e6a9e7981723
Roberts, Angharad M.
ff1e5c2c-db47-4224-9cbc-4dce0e57db43
Brady, Angela F.
6a592734-d3ec-40dd-a159-f157cd8f56eb
Foulds, Nicki
5e153e9f-caae-45f5-b6f0-943bd567558e
Bewes, Beverley
3d53eb7b-8ea1-423a-87fc-1394b4c79379
Volleth, Marianne
4093d3ae-8b56-4da9-9334-bae514c73389
Liehr, Thomas
b99d17d3-69ab-4bac-8774-5d21177abcda
Mehnert, Karl
52207df7-d1f7-42d4-9972-5709eaacf8db
Bateman, Mark
1fdbeb26-4d05-4ba7-80ce-f16680ddcad9
White, Helen
d5aff204-b128-46c8-8aab-c9be75a97e70

Barber, John C.K., Hall, Victoria, Maloney, Viv K., Huang, Shuwen, Roberts, Angharad M., Brady, Angela F., Foulds, Nicki, Bewes, Beverley, Volleth, Marianne, Liehr, Thomas, Mehnert, Karl, Bateman, Mark and White, Helen (2013) 16p11.2–p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2. European Journal of Human Genetics, 21 (2), 182-189. (doi:10.1038/ejhg.2012.144). (PMID:22828807)

Record type: Article

Abstract

Chromosome 16 contains multiple copy number variations (CNVs) that predispose to genomic disorders. Here, we differentiate pathogenic duplications of 16p11.2–p12.2 from microscopically similar euchromatic variants of 16p11.2. Patient 1 was a girl of 18 with autism, moderate intellectual disability, behavioural difficulties, dysmorphic features and a 7.71-Mb (megabase pair) duplication (16:21?521?005–29?233?146). Patient 2 had a 7.81-Mb duplication (16:21?382?561–29?191?527), speech delay and obsessional behaviour as a boy and, as an adult, short stature, macrocephaly and mild dysmorphism. The duplications contain 65 coding genes of which Polo-like kinase 1 (PLK1) has the highest likelihood of being haploinsufficient and, by implication, a triplosensitive gene. An additional 1.11-Mb CNV of 10q11.21 in Patient 1 was a possible modifier containing the G-protein-regulated inducer of neurite growth 2 (GPRIN2) gene. In contrast, the euchromatic variants in Patients 3 and 4 were amplifications from a 945-kb region containing non-functional immunoglobulin heavy chain (IGHV), hect domain pseudogene (HERC2P4) and TP53-inducible target gene 3 (TP53TG3) loci in proximal 16p11.2 (16:31?953?353–32?898?635). Paralogous pyrosequencing gave a total copy number of 3–8 in controls and 8 to >10 in Patients 3 and 4. The 16p11.2–p12.2 duplication syndrome is a recurrent genomic disorder with a variable phenotype including developmental delay, dysmorphic features, mild to severe intellectual disability, autism, obsessive or stereotyped behaviour, short stature and anomalies of the hands and fingers. It is important to differentiate pathogenic 16p11.2–p12.2 duplications from harmless, microscopically similar euchromatic variants of proximal 16p11.2, especially at prenatal diagnosis

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e-pub ahead of print date: 25 July 2012
Published date: February 2013
Organisations: Human Development & Health

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Local EPrints ID: 341573
URI: https://eprints.soton.ac.uk/id/eprint/341573
ISSN: 1018-4813
PURE UUID: a5ee6825-ce71-4098-a6a7-fcf640f62720

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Date deposited: 27 Jul 2012 14:06
Last modified: 09 Feb 2018 17:31

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Contributors

Author: John C.K. Barber
Author: Victoria Hall
Author: Viv K. Maloney
Author: Shuwen Huang
Author: Angharad M. Roberts
Author: Angela F. Brady
Author: Nicki Foulds
Author: Beverley Bewes
Author: Marianne Volleth
Author: Thomas Liehr
Author: Karl Mehnert
Author: Mark Bateman
Author: Helen White

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