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A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

Background The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Met... Full description

Journal Title: Journal of medical genetics 2012-10, Vol.49 (10), p.660-668
Main Author: Zufferey, Flore
Other Authors: Sherr, Elliott H , Beckmann, Noam D , Hanson, Ellen , Maillard, Anne M , Hippolyte, Loyse , Macé, Aurélien , Ferrari, Carina , Kutalik, Zoltán , Andrieux, Joris , Aylward, Elizabeth , Barker, Mandy , Bernier, Raphael , Bouquillon, Sonia , Conus, Philippe , Delobel, Bruno , Faucett, W Andrew , Goin-Kochel, Robin P , Grant, Ellen , Harewood, Louise , Hunter, Jill V , Lebon, Sébastien , Ledbetter, David H , Martin, Christa Lese , Männik, Katrin , Martinet, Danielle , Mukherjee, Pratik , Ramocki, Melissa B , Spence, Sarah J , Steinman, Kyle J , Tjernagel, Jennifer , Spiro, John E , Reymond, Alexandre , Beckmann, Jacques S , Chung, Wendy K , Jacquemont, Sébastien
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Language: English
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Quelle: Alma/SFX Local Collection
Publisher: London: BMJ Publishing Group Ltd
ID: ISSN: 0022-2593
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title: A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
format: Article
creator:
  • Zufferey, Flore
  • Sherr, Elliott H
  • Beckmann, Noam D
  • Hanson, Ellen
  • Maillard, Anne M
  • Hippolyte, Loyse
  • Macé, Aurélien
  • Ferrari, Carina
  • Kutalik, Zoltán
  • Andrieux, Joris
  • Aylward, Elizabeth
  • Barker, Mandy
  • Bernier, Raphael
  • Bouquillon, Sonia
  • Conus, Philippe
  • Delobel, Bruno
  • Faucett, W Andrew
  • Goin-Kochel, Robin P
  • Grant, Ellen
  • Harewood, Louise
  • Hunter, Jill V
  • Lebon, Sébastien
  • Ledbetter, David H
  • Martin, Christa Lese
  • Männik, Katrin
  • Martinet, Danielle
  • Mukherjee, Pratik
  • Ramocki, Melissa B
  • Spence, Sarah J
  • Steinman, Kyle J
  • Tjernagel, Jennifer
  • Spiro, John E
  • Reymond, Alexandre
  • Beckmann, Jacques S
  • Chung, Wendy K
  • Jacquemont, Sébastien
subjects:
  • 1506
  • Adolescent
  • Adult
  • Biological and medical sciences
  • Body Mass Index
  • Child
  • Child Development Disorders
  • Child Development Disorders, Pervasive - diagnosis
  • Child Development Disorders, Pervasive - genetics
  • Chromosome Deletion
  • Chromosomes
  • Chromosomes, Human, Pair 16
  • Clinical genetics
  • Complex traits
  • Copy
  • Copy-Number Variation
  • Developmental Disabilities
  • Developmental Disabilities - diagnosis
  • Developmental Disabilities - genetics
  • diagnosis
  • Female
  • Fundamental and applied biological sciences. Psychology
  • Gene Order
  • genetics
  • Genetics of eukaryotes. Biological and molecular evolution
  • Heterozygote
  • Human
  • Human medicine
  • Humans
  • Intelligence Tests
  • Life Sciences
  • Male
  • Medical genetics
  • Medical sciences
  • Molecular and cellular biology
  • Number Variation
  • Obesity
  • Pair 16
  • Pervasive
  • Phenotype
  • Psychiatry
  • Syndrome
  • Young Adult
ispartof: Journal of medical genetics, 2012-10, Vol.49 (10), p.660-668
description: Background The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0022-2593
fulltext: fulltext
issn:
  • 0022-2593
  • 1468-6244
url: Link


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titleA 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
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creatorZufferey, Flore ; Sherr, Elliott H ; Beckmann, Noam D ; Hanson, Ellen ; Maillard, Anne M ; Hippolyte, Loyse ; Macé, Aurélien ; Ferrari, Carina ; Kutalik, Zoltán ; Andrieux, Joris ; Aylward, Elizabeth ; Barker, Mandy ; Bernier, Raphael ; Bouquillon, Sonia ; Conus, Philippe ; Delobel, Bruno ; Faucett, W Andrew ; Goin-Kochel, Robin P ; Grant, Ellen ; Harewood, Louise ; Hunter, Jill V ; Lebon, Sébastien ; Ledbetter, David H ; Martin, Christa Lese ; Männik, Katrin ; Martinet, Danielle ; Mukherjee, Pratik ; Ramocki, Melissa B ; Spence, Sarah J ; Steinman, Kyle J ; Tjernagel, Jennifer ; Spiro, John E ; Reymond, Alexandre ; Beckmann, Jacques S ; Chung, Wendy K ; Jacquemont, Sébastien
creatorcontribZufferey, Flore ; Sherr, Elliott H ; Beckmann, Noam D ; Hanson, Ellen ; Maillard, Anne M ; Hippolyte, Loyse ; Macé, Aurélien ; Ferrari, Carina ; Kutalik, Zoltán ; Andrieux, Joris ; Aylward, Elizabeth ; Barker, Mandy ; Bernier, Raphael ; Bouquillon, Sonia ; Conus, Philippe ; Delobel, Bruno ; Faucett, W Andrew ; Goin-Kochel, Robin P ; Grant, Ellen ; Harewood, Louise ; Hunter, Jill V ; Lebon, Sébastien ; Ledbetter, David H ; Martin, Christa Lese ; Männik, Katrin ; Martinet, Danielle ; Mukherjee, Pratik ; Ramocki, Melissa B ; Spence, Sarah J ; Steinman, Kyle J ; Tjernagel, Jennifer ; Spiro, John E ; Reymond, Alexandre ; Beckmann, Jacques S ; Chung, Wendy K ; Jacquemont, Sébastien ; Simons VIP Consortium ; 16p11.2 European Consortium ; on behalf of the Simons VIP Consortium ; on behalf of the 16p11.2 European Consortium
descriptionBackground The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
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languageeng
publisherLondon: BMJ Publishing Group Ltd
subject1506 ; Adolescent ; Adult ; Biological and medical sciences ; Body Mass Index ; Child ; Child Development Disorders ; Child Development Disorders, Pervasive - diagnosis ; Child Development Disorders, Pervasive - genetics ; Chromosome Deletion ; Chromosomes ; Chromosomes, Human, Pair 16 ; Clinical genetics ; Complex traits ; Copy ; Copy-Number Variation ; Developmental Disabilities ; Developmental Disabilities - diagnosis ; Developmental Disabilities - genetics ; diagnosis ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Order ; genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Heterozygote ; Human ; Human medicine ; Humans ; Intelligence Tests ; Life Sciences ; Male ; Medical genetics ; Medical sciences ; Molecular and cellular biology ; Number Variation ; Obesity ; Pair 16 ; Pervasive ; Phenotype ; Psychiatry ; Syndrome ; Young Adult
ispartofJournal of medical genetics, 2012-10, Vol.49 (10), p.660-668
rights
0Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
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3Copyright: 2012 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
4Distributed under a Creative Commons Attribution 4.0 International License
5Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions 2012
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0Zufferey, Flore
1Sherr, Elliott H
2Beckmann, Noam D
3Hanson, Ellen
4Maillard, Anne M
5Hippolyte, Loyse
6Macé, Aurélien
7Ferrari, Carina
8Kutalik, Zoltán
9Andrieux, Joris
10Aylward, Elizabeth
11Barker, Mandy
12Bernier, Raphael
13Bouquillon, Sonia
14Conus, Philippe
15Delobel, Bruno
16Faucett, W Andrew
17Goin-Kochel, Robin P
18Grant, Ellen
19Harewood, Louise
20Hunter, Jill V
21Lebon, Sébastien
22Ledbetter, David H
23Martin, Christa Lese
24Männik, Katrin
25Martinet, Danielle
26Mukherjee, Pratik
27Ramocki, Melissa B
28Spence, Sarah J
29Steinman, Kyle J
30Tjernagel, Jennifer
31Spiro, John E
32Reymond, Alexandre
33Beckmann, Jacques S
34Chung, Wendy K
35Jacquemont, Sébastien
36Simons VIP Consortium
3716p11.2 European Consortium
38on behalf of the Simons VIP Consortium
39on behalf of the 16p11.2 European Consortium
title
0A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
1Journal of medical genetics
addtitleJ Med Genet
descriptionBackground The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
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12Clinical genetics
13Complex traits
14Copy
15Copy-Number Variation
16Developmental Disabilities
17Developmental Disabilities - diagnosis
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21Fundamental and applied biological sciences. Psychology
22Gene Order
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24Genetics of eukaryotes. Biological and molecular evolution
25Heterozygote
26Human
27Human medicine
28Humans
29Intelligence Tests
30Life Sciences
31Male
32Medical genetics
33Medical sciences
34Molecular and cellular biology
35Number Variation
36Obesity
37Pair 16
38Pervasive
39Phenotype
40Psychiatry
41Syndrome
42Young Adult
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8Kutalik, Zoltán
9Andrieux, Joris
10Aylward, Elizabeth
11Barker, Mandy
12Bernier, Raphael
13Bouquillon, Sonia
14Conus, Philippe
15Delobel, Bruno
16Faucett, W Andrew
17Goin-Kochel, Robin P
18Grant, Ellen
19Harewood, Louise
20Hunter, Jill V
21Lebon, Sébastien
22Ledbetter, David H
23Martin, Christa Lese
24Männik, Katrin
25Martinet, Danielle
26Mukherjee, Pratik
27Ramocki, Melissa B
28Spence, Sarah J
29Steinman, Kyle J
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titleA 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
authorZufferey, Flore ; Sherr, Elliott H ; Beckmann, Noam D ; Hanson, Ellen ; Maillard, Anne M ; Hippolyte, Loyse ; Macé, Aurélien ; Ferrari, Carina ; Kutalik, Zoltán ; Andrieux, Joris ; Aylward, Elizabeth ; Barker, Mandy ; Bernier, Raphael ; Bouquillon, Sonia ; Conus, Philippe ; Delobel, Bruno ; Faucett, W Andrew ; Goin-Kochel, Robin P ; Grant, Ellen ; Harewood, Louise ; Hunter, Jill V ; Lebon, Sébastien ; Ledbetter, David H ; Martin, Christa Lese ; Männik, Katrin ; Martinet, Danielle ; Mukherjee, Pratik ; Ramocki, Melissa B ; Spence, Sarah J ; Steinman, Kyle J ; Tjernagel, Jennifer ; Spiro, John E ; Reymond, Alexandre ; Beckmann, Jacques S ; Chung, Wendy K ; Jacquemont, Sébastien
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35Number Variation
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39Phenotype
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26Mukherjee, Pratik
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30Tjernagel, Jennifer
31Spiro, John E
32Reymond, Alexandre
33Beckmann, Jacques S
34Chung, Wendy K
35Jacquemont, Sébastien
aucorp
0Simons VIP Consortium
116p11.2 European Consortium
2on behalf of the Simons VIP Consortium
3on behalf of the 16p11.2 European Consortium
formatjournal
genrearticle
ristypeJOUR
atitleA 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
jtitleJournal of medical genetics
addtitleJ Med Genet
date2012-10
risdate2012
volume49
issue10
spage660
epage668
pages660-668
issn0022-2593
eissn1468-6244
codenJMDGAE
notes
0FZ, EHS, NDB, EH: equally contributing first authors.
1PMCID: PMC3494011
2AR, JSB, WKC, SJ: equally contributing senior authors.
abstractBackground The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
copLondon
pubBMJ Publishing Group Ltd
pmid23054248
doi10.1136/jmedgenet-2012-101203
oafree_for_read