Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Maria Delio; Tingwei Guo; Donna M McDonald-McGinn; Elaine Zackai; Sean Herman; Mark Kaminetzky; Anne Marie Higgins; Karlene Coleman; Carolyn Chow; Maria Jalbrzikowski; Maria Jarlbrzkowski; Carrie E Bearden; Alice Bailey; Anders Vangkilde; Line Olsen; Charlotte Olesen; Flemming Skovby; Thomas M Werge; Ludivine Templin; Tiffany Busa; Nicole Philip; Ann Swillen; Joris R Vermeesch; Koen Devriendt; Maude Schneider; Sophie Dahoun; Stephan Eliez; Kelly Schoch; Stephen R Hooper; Vandana Shashi; Joy Samanich; Robert Marion; Therese van Amelsvoort; Erik Boot; Petra Klaassen; Sasja N Duijff; Jacob Vorstman; Tracy Yuen; Candice Silversides; Eva Chow; Anne Bassett; Amos Frisch; Abraham Weizman; Doron Gothelf; Maria Niarchou; Marianne van den Bree; Michael J Owen; Damian Heine Su�er; Jordi Rosell Andreo; Marco Armando; Stefano Vicari; Maria Cristina Digilio; Adam Auton; Wendy R Kates; Tao Wang; Robert J Shprintzen; Beverly S Emanuel; Bernice E Morrow

doi:10.1016/j.ajhg.2013.01.018

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Maria Delio, Tingwei Guo, Donna M McDonald-McGinn, Elaine Zackai, Sean Herman, Mark Kaminetzky, Anne Marie Higgins, Karlene Coleman, Carolyn Chow, Maria Jalbrzikowski, Maria Jarlbrzkowski, Carrie E Bearden, Alice Bailey, Anders Vangkilde, Line Olsen, Charlotte Olesen, Flemming Skovby, Thomas M Werge, Ludivine Templin, Tiffany BusaNicole Philip, Ann Swillen, Joris R Vermeesch, Koen Devriendt, Maude Schneider, Sophie Dahoun, Stephan Eliez, Kelly Schoch, Stephen R Hooper, Vandana Shashi, Joy Samanich, Robert Marion, Therese van Amelsvoort, Erik Boot, Petra Klaassen, Sasja N Duijff, Jacob Vorstman, Tracy Yuen, Candice Silversides, Eva Chow, Anne Bassett, Amos Frisch, Abraham Weizman, Doron Gothelf, Maria Niarchou, Marianne van den Bree, Michael J Owen, Damian Heine Su�er, Jordi Rosell Andreo, Marco Armando, Stefano Vicari, Maria Cristina Digilio, Adam Auton, Wendy R Kates, Tao Wang, Robert J Shprintzen, Beverly S Emanuel, Bernice E Morrow

37 Citationer (Scopus)

Abstract

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.

Originalsprog	Engelsk
Tidsskrift	American Journal of Human Genetics
Vol/bind	92
Udgave nummer	3
Sider (fra-til)	439-47
Antal sider	9
ISSN	0002-9297
DOI	https://doi.org/10.1016/j.ajhg.2013.01.018
Status	Udgivet - 7 mar. 2013

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10.1016/j.ajhg.2013.01.018

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Delio, M., Guo, T., McDonald-McGinn, D. M., Zackai, E., Herman, S., Kaminetzky, M., Higgins, A. M., Coleman, K., Chow, C., Jalbrzikowski, M., Jarlbrzkowski, M., Bearden, C. E., Bailey, A., Vangkilde, A., Olsen, L., Olesen, C., Skovby, F., Werge, T. M., Templin, L., ... Morrow, B. E. (2013). Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes. American Journal of Human Genetics, 92(3), 439-47. https://doi.org/10.1016/j.ajhg.2013.01.018

Delio, M, Guo, T, McDonald-McGinn, DM, Zackai, E, Herman, S, Kaminetzky, M, Higgins, AM, Coleman, K, Chow, C, Jalbrzikowski, M, Jarlbrzkowski, M, Bearden, CE, Bailey, A, Vangkilde, A, Olsen, L, Olesen, C, Skovby, F, Werge, TM, Templin, L, Busa, T, Philip, N, Swillen, A, Vermeesch, JR, Devriendt, K, Schneider, M, Dahoun, S, Eliez, S, Schoch, K, Hooper, SR, Shashi, V, Samanich, J, Marion, R, van Amelsvoort, T, Boot, E, Klaassen, P, Duijff, SN, Vorstman, J, Yuen, T, Silversides, C, Chow, E, Bassett, A, Frisch, A, Weizman, A, Gothelf, D, Niarchou, M, van den Bree, M, Owen, MJ, Su�er, DH, Andreo, JR, Armando, M, Vicari, S, Digilio, MC, Auton, A, Kates, WR, Wang, T, Shprintzen, RJ, Emanuel, BS & Morrow, BE 2013, 'Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes', American Journal of Human Genetics, bind 92, nr. 3, s. 439-47. https://doi.org/10.1016/j.ajhg.2013.01.018

@article{cb3d552c3bf14f37980015a5914e5d92,

title = "Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes",

abstract = "Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.",

author = "Maria Delio and Tingwei Guo and McDonald-McGinn, {Donna M} and Elaine Zackai and Sean Herman and Mark Kaminetzky and Higgins, {Anne Marie} and Karlene Coleman and Carolyn Chow and Maria Jalbrzikowski and Maria Jarlbrzkowski and Bearden, {Carrie E} and Alice Bailey and Anders Vangkilde and Line Olsen and Charlotte Olesen and Flemming Skovby and Werge, {Thomas M} and Ludivine Templin and Tiffany Busa and Nicole Philip and Ann Swillen and Vermeesch, {Joris R} and Koen Devriendt and Maude Schneider and Sophie Dahoun and Stephan Eliez and Kelly Schoch and Hooper, {Stephen R} and Vandana Shashi and Joy Samanich and Robert Marion and {van Amelsvoort}, Therese and Erik Boot and Petra Klaassen and Duijff, {Sasja N} and Jacob Vorstman and Tracy Yuen and Candice Silversides and Eva Chow and Anne Bassett and Amos Frisch and Abraham Weizman and Doron Gothelf and Maria Niarchou and {van den Bree}, Marianne and Owen, {Michael J} and Su�er, {Damian Heine} and Andreo, {Jordi Rosell} and Marco Armando and Stefano Vicari and Digilio, {Maria Cristina} and Adam Auton and Kates, {Wendy R} and Tao Wang and Shprintzen, {Robert J} and Emanuel, {Beverly S} and Morrow, {Bernice E}",

year = "2013",

month = mar,

day = "7",

doi = "10.1016/j.ajhg.2013.01.018",

language = "English",

volume = "92",

pages = "439--47",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

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TY - JOUR

T1 - Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

AU - Delio, Maria

AU - Guo, Tingwei

AU - McDonald-McGinn, Donna M

AU - Zackai, Elaine

AU - Herman, Sean

AU - Kaminetzky, Mark

AU - Higgins, Anne Marie

AU - Coleman, Karlene

AU - Chow, Carolyn

AU - Jalbrzikowski, Maria

AU - Jarlbrzkowski, Maria

AU - Bearden, Carrie E

AU - Bailey, Alice

AU - Vangkilde, Anders

AU - Olsen, Line

AU - Olesen, Charlotte

AU - Skovby, Flemming

AU - Werge, Thomas M

AU - Templin, Ludivine

AU - Busa, Tiffany

AU - Philip, Nicole

AU - Swillen, Ann

AU - Vermeesch, Joris R

AU - Devriendt, Koen

AU - Schneider, Maude

AU - Dahoun, Sophie

AU - Eliez, Stephan

AU - Schoch, Kelly

AU - Hooper, Stephen R

AU - Shashi, Vandana

AU - Samanich, Joy

AU - Marion, Robert

AU - van Amelsvoort, Therese

AU - Boot, Erik

AU - Klaassen, Petra

AU - Duijff, Sasja N

AU - Vorstman, Jacob

AU - Yuen, Tracy

AU - Silversides, Candice

AU - Chow, Eva

AU - Bassett, Anne

AU - Frisch, Amos

AU - Weizman, Abraham

AU - Gothelf, Doron

AU - Niarchou, Maria

AU - van den Bree, Marianne

AU - Owen, Michael J

AU - Su�er, Damian Heine

AU - Andreo, Jordi Rosell

AU - Armando, Marco

AU - Vicari, Stefano

AU - Digilio, Maria Cristina

AU - Auton, Adam

AU - Kates, Wendy R

AU - Wang, Tao

AU - Shprintzen, Robert J

AU - Emanuel, Beverly S

AU - Morrow, Bernice E

PY - 2013/3/7

Y1 - 2013/3/7

N2 - Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.

AB - Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.

U2 - 10.1016/j.ajhg.2013.01.018

DO - 10.1016/j.ajhg.2013.01.018

M3 - Journal article

C2 - 23453669

SN - 0002-9297

VL - 92

SP - 439

EP - 447

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

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