Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes.

نویسندگان

  • Maria Delio
  • Tingwei Guo
  • Donna M McDonald-McGinn
  • Elaine Zackai
  • Sean Herman
  • Mark Kaminetzky
  • Anne Marie Higgins
  • Karlene Coleman
  • Carolyn Chow
  • Maria Jalbrzikowski
  • 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 Suñer
  • 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
چکیده

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.

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منابع مشابه

22q11.2 deletion syndrome

DiGeorge and velocardiofacial syndrome (22q11.2 deletion syndrome) is the most common microdeletion disorder in humans and, hence, one of the most common multiple malformation syndromes, with an estimated prevalence of 1 in 2000 to 1 in 4000. It is characterized by craniofacial anomalies, conotruncal heart disease, thymic aplasia and hypoplasia, hypocalcemia, and psychiatric illness. In this ar...

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Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study.

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Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features.

Cytogenetic and FISH analysis was performed in 139 patients to detect the pathognomonic of Di George/ Velocardiofacial syndrome (DGS/VFCS) deletion 22q11.2. An abnormal karyotype was revealed in 2/139 cases (47, XXY and 46, XX, 2p+). A deletion was found in 17/139 (12.2%) patients (14 males/ 3 females), inherited in 3 (2 maternal and 1 paternal). Patients with 22q11.2 deletion exhibited facial ...

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Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

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Language skills in children with velocardiofacial syndrome (deletion 22q11.2).

OBJECTIVE To further define the language profile of children with velocardiofacial syndrome (VCFS) and explore the influence of parental origin of the deletion on language. STUDY DESIGN Children and adolescents with VCFS (n = 27) were group-matched for sex, age, and IQ with 27 children and adolescents with idiopathic developmental delay. Fifty-four typically developing control subjects were a...

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عنوان ژورنال:
  • American journal of human genetics

دوره 92 3  شماره 

صفحات  -

تاریخ انتشار 2013