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

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• 作者：Maria Delio¹ ; Tingwei Guo¹ ; Donna M. McDonald-McGinn² ; ³ ; Elaine Zackai² ; ³ ; ⁴ ; Sean Herman¹ ; Mark Kaminetzky¹ ; Anne Marie Higgins⁵ ; Karlene Coleman⁶ ; ⁷ ; Carolyn Chow⁸ ; Maria Jarlbrzkowski⁸ ; Carrie E. Bearden⁸ ; Alice Bailey² ; ³ ; Anders Vangkilde⁹ ; Line Olsen⁹ ; Charlotte Olesen¹⁰ ; Flemming Skovby¹¹ ; Thomas M. Werge⁹ ; Ludivine Templin¹¹ ; Tiffany Busa¹¹ ; Nicole Philip¹² ; Ann Swillen¹³ ; Joris R. Vermeesch¹³ ; Koen Devriendt¹³ ; Maude Schneider¹⁴ ; Sophie Dahoun¹⁴ ; Stephan Eliez¹⁴ ; Kelly Schoch¹⁵ ; Stephen R. Hooper¹⁶ ; ¹⁷ ; Vandana Shashi¹⁵ ; Joy Samanich¹⁸ ; Robert Marion¹⁸ ; Therese van Amelsvoort¹⁹ ; Erik Boot²⁰ ; Petra Klaassen²¹ ; Sasja N. Duijff²¹ ; Jacob Vorstman²² ; Tracy Yuen²³ ; Candice Silversides²³ ; Eva Chow²³ ; Anne Bassett²³ ; Amos Frisch²⁴ ; Abraham Weizman²⁵ ; Doron Gothelf²⁵ ; ²⁶ ; Maria Niarchou²⁷ ; Marianne van den Bree²⁷ ; Michael J. Owen²⁷ ; Damian Heine Suñ ; er²⁸ ; Jordi Rosell Andreo²⁸ ; Marco Armando²⁹ ; Stefano Vicari²⁹ ; Maria Cristina Digilio³⁰ ; Adam Auton³¹ ; Wendy R. Kates³² ; Tao Wang³³ ; Robert J. Shprintzen⁵ ; Beverly S. Emanuel² ; ³ ; ⁴ ; Bernice E. Morrow¹ ; ³⁴ ; ^{bernice.morrow@einstein.yu.edu}
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：7 March, 2013
• 年：2013
• 卷：92
• 期：3
• 页码：439-447
• 全文大小：902 K

文摘

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.