Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism
Christian P. Schaaf,Manuel L. Gonzalez-Garay,Fan Xia,Lorraine Potocki,Karen W. Gripp,Baili Zhang,Brock A. Peters,Mark A. McElwain,Radoje Drmanac,Arthur L. Beaudet,C. Thomas Caskey,Yaping Yang +11 more
Reads0
Chats0
TLDR
Findings suggest that MAGEL2 is a new gene causing complex ASD and thatMAGEL2 loss of function can contribute to several aspects of the PWS phenotype.Abstract:
Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed, maternally silenced genes at 15q11-q13 We report four individuals with truncating mutations on the paternal allele of MAGEL2, a gene within the PWS domain The first subject was ascertained by whole-genome sequencing analysis for PWS features Three additional subjects were identified by reviewing the results of exome sequencing of 1,248 cases in a clinical laboratory All four subjects had autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of PWS These findings suggest that MAGEL2 is a new gene causing complex ASD and that MAGEL2 loss of function can contribute to several aspects of the PWS phenotyperead more
Citations
More filters
Journal ArticleDOI
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
John R. B. Perry,Felix R. Day,Cathy E. Elks,Patrick Sulem,Deborah J. Thompson,Teresa Ferreira,Chunyan He,Daniel I. Chasman,Tõnu Esko,Tõnu Esko,Gudmar Thorleifsson,Eva Albrecht,Wei Ang,Tanguy Corre,Tanguy Corre,Diana L. Cousminer,Bjarke Feenstra,Nora Franceschini,Andrea Ganna,Andrew D. Johnson,Sanela Kjellqvist,Kathryn L. Lunetta,George McMahon,Ilja M. Nolte,Lavinia Paternoster,Eleonora Porcu,Albert V. Smith,Lisette Stolk,Alexander Teumer,Natalia Tšernikova,Emmi Tikkanen,Sheila Ulivi,Erin K. Wagner,Najaf Amin,Laura J. Bierut,Enda M. Byrne,Enda M. Byrne,Jouke-Jan Hottenga,Daniel L. Koller,Massimo Mangino,Tune H. Pers,Tune H. Pers,Tune H. Pers,Laura M. Yerges-Armstrong,Jing Hua Zhao,Irene L. Andrulis,Hoda Anton-Culver,Femke Atsma,Stefania Bandinelli,Matthias W. Beckmann,Javier Benitez,Carl Blomqvist,Stig E. Bojesen,Manjeet K. Bolla,Bernardo Bonanni,Hiltrud Brauch,Hiltrud Brauch,Hermann Brenner,Julie E. Buring,Jenny Chang-Claude,Stephen J. Chanock,Jinhui Chen,Georgia Chenevix-Trench,J. Margriet Collée,Fergus J. Couch,David Couper,Andrea D. Coviello,Angela Cox,Kamila Czene,Adamo Pio D'Adamo,George Davey Smith,Immaculata De Vivo,Ellen W. Demerath,Joe Dennis,Peter Devilee,Aida Karina Dieffenbach,Alison M. Dunning,Gudny Eiriksdottir,Johan G. Eriksson,Johan G. Eriksson,Peter A. Fasching,Luigi Ferrucci,Dieter Flesch-Janys,Henrik Flyger,Tatiana Foroud,Lude Franke,Melissa E. Garcia,Montserrat Garcia-Closas,Frank Geller,Eco de Geus,Graham G. Giles,Graham G. Giles,Daniel F. Gudbjartsson,Daniel F. Gudbjartsson,Vilmundur Gudnason,Pascal Guénel,Suiqun Guo,Per Hall,Ute Hamann,Robin Haring,Catharina A. Hartman,Andrew C. Heath,Albert Hofman,Maartje J. Hooning,John L. Hopper,Frank B. Hu,David J. Hunter,David Karasik,Douglas P. Kiel,Julia A. Knight,Veli-Matti Kosma,Zoltán Kutalik,Zoltán Kutalik,Sandra Lai,Diether Lambrechts,Annika Lindblom,Reedik Mägi,Patrik K. E. Magnusson,Arto Mannermaa,Nicholas G. Martin,Gisli Masson,Patrick F. McArdle,Wendy L. McArdle,Mads Melbye,Mads Melbye,Kyriaki Michailidou,Evelin Mihailov,Lili Milani,Roger L. Milne,Roger L. Milne,Heli Nevanlinna,Patrick Neven,Ellen A. Nohr,Albertine J. Oldehinkel,Ben A. Oostra,Aarno Palotie,Aarno Palotie,Aarno Palotie,Munro Peacock,Nancy L. Pedersen,Paolo Peterlongo,Julian Peto,Paul D.P. Pharoah,Dirkje S. Postma,Anneli Pouta,Anneli Pouta,Katri Pylkäs,Paolo Radice,Susan M. Ring,Fernando Rivadeneira,Antonietta Robino,Lynda M. Rose,Anja Rudolph,Veikko Salomaa,Serena Sanna,David Schlessinger,Marjanka K. Schmidt,Mellissa C. Southey,Ulla Sovio,Ulla Sovio,Meir J. Stampfer,Doris Stöckl,Anna Maria Storniolo,Nicholas J. Timpson,Jonathan Tyrer,Jenny A. Visser,Peter Vollenweider,Henry Völzke,Gérard Waeber,Melanie Waldenberger,Henri Wallaschofski,Qin Wang,Gonneke Willemsen,Robert Winqvist,Bruce H. R. Wolffenbuttel,Margaret J. Wright,Dorret I. Boomsma,Michael J. Econs,Kay-Tee Khaw,Ruth J. F. Loos,Ruth J. F. Loos,Mark I. McCarthy,Grant W. Montgomery,John P. Rice,Elizabeth A. Streeten,Elizabeth A. Streeten,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Cornelia M. van Duijn,Behrooz Z. Alizadeh,Sven Bergmann,Sven Bergmann,Eric Boerwinkle,Heather A. Boyd,Laura Crisponi,Paolo Gasparini,Christian Gieger,Tamara B. Harris,Erik Ingelsson,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Peter Kraft,Debbie A Lawlor,Andres Metspalu,Craig E. Pennell,Paul M. Ridker,Harold Snieder,Thorkild I. A. Sørensen,Tim D. Spector,David P. Strachan,André G. Uitterlinden,Nicholas J. Wareham,Elisabeth Widen,Marek Zygmunt,Anna Murray,Douglas F. Easton,Kari Stefansson,Kari Stefansson,Joanne M. Murabito,Ken K. Ong +220 more
TL;DR: In this article, the authors used genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies and found robust evidence for 123 signals at 106 genomic loci associated with age at menarche.
Journal ArticleDOI
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders
Sarah E Soden,Sarah E Soden,Carol J Saunders,Laurel K. Willig,Laurel K. Willig,Emily G. Farrow,Laurie D. Smith,Laurie D. Smith,Josh E Petrikin,Josh E Petrikin,Jean Baptiste LePichon,Jean Baptiste LePichon,Neil A. Miller,Isabelle Thiffault,Darrell L. Dinwiddie,Greyson P Twist,Aaron Noll,Bryce A. Heese,Lee Zellmer,Andrea M. Atherton,Andrea M. Atherton,Ahmed Abdelmoity,Nicole P. Safina,Sarah S. Nyp,Britton Zuccarelli,Ingrid A. Larson,Ann C. Modrcin,Suzanne Herd,Mitchell Creed,Zhaohui Ye,Xuan Yuan,Robert A. Brodsky,Stephen F. Kingsmore +32 more
TL;DR: It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients.
Journal ArticleDOI
Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings
TL;DR: Updated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.
Journal ArticleDOI
The role of genomic imprinting in biology and disease: an expanding view
TL;DR: It is shown that imprinted genes influence an extraordinarily wide-ranging array of biological processes, the effects of which extend into adulthood, and play important parts in common diseases that range from obesity to psychiatric disorders.
Journal ArticleDOI
Epigenetics and Human Disease.
Huda Y. Zoghbi,Arthur L. Beaudet +1 more
TL;DR: Research that has uncovered human diseases that stem from epigenetic deregulation, including disease-causing genetic mutations in epigenetic modifiers that either affect chromatin in trans or have a cis effect in altering chromatin configuration is described.
References
More filters
Journal ArticleDOI
Systematic Review: Process of Forming Academic Service Partnerships to Reform Clinical Education
TL;DR: This study’s findings can provide practical guidelines to steer partnership programs within the academic and clinical bodies, with the aim of providing a collaborative partnership approach to clinical education.
Journal ArticleDOI
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
Brian J. O'Roak,Laura Vives,Santhosh Girirajan,Emre Karakoc,Niklas Krumm,Bradley P. Coe,Roie Levy,Arthur Ko,Choli Lee,Joshua D. Smith,Emily H. Turner,Ian B. Stanaway,Benjamin Vernot,Maika Malig,Carl Baker,Beau Reilly,Joshua M. Akey,Elhanan Borenstein,Elhanan Borenstein,Mark J. Rieder,Deborah A. Nickerson,Raphael Bernier,Jay Shendure,Evan E. Eichler,Evan E. Eichler +24 more
TL;DR: It is shown that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD.
Journal ArticleDOI
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Stephen Sanders,Michael T. Murtha,Abha R. Gupta,John D. Murdoch,Melanie J. Raubeson,A. Jeremy Willsey,A. Gulhan Ercan-Sencicek,Nicholas M. DiLullo,Neelroop N. Parikshak,Jason L. Stein,Michael F. Walker,Gordon T. Ober,Nicole A. Teran,Youeun Song,Paul El-Fishawy,Ryan C. Murtha,Murim Choi,John D. Overton,Robert D. Bjornson,Nicholas Carriero,Kyle A. Meyer,Kaya Bilguvar,Shrikant Mane,Nenad Sestan,Richard P. Lifton,Murat Gunel,Kathryn Roeder,Daniel H. Geschwind,Bernie Devlin,Matthew W. State +29 more
TL;DR: It is shown, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects.
Journal ArticleDOI
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Benjamin M. Neale,Yan Kou,Li Liu,Avi Ma'ayan,Kaitlin E. Samocha,Kaitlin E. Samocha,Aniko Sabo,Chiao-Feng Lin,Christine Stevens,Li-San Wang,Vladimir Makarov,Paz Polak,Paz Polak,Seungtai Yoon,Jared Maguire,Emily L. Crawford,Nicholas G. Campbell,Evan T. Geller,Otto Valladares,Chad M. Schafer,Han Liu,Tuo Zhao,Guiqing Cai,Jayon Lihm,Ruth Dannenfelser,Omar Jabado,Zuleyma Peralta,Uma Nagaswamy,Donna M. Muzny,Jeffrey G. Reid,Irene Newsham,Yuanqing Wu,Lora Lewis,Yi Han,Benjamin F. Voight,Benjamin F. Voight,Elaine T. Lim,Elaine T. Lim,Elizabeth J. Rossin,Elizabeth J. Rossin,Andrew Kirby,Andrew Kirby,Jason Flannick,Menachem Fromer,Menachem Fromer,Khalid Shakir,Timothy Fennell,Kiran V. Garimella,Eric Banks,Ryan Poplin,Stacey Gabriel,Mark A. DePristo,Jack R. Wimbish,Braden E. Boone,Shawn Levy,Catalina Betancur,Shamil R. Sunyaev,Shamil R. Sunyaev,Eric Boerwinkle,Eric Boerwinkle,Joseph D. Buxbaum,Edwin H. Cook,Bernie Devlin,Richard A. Gibbs,Kathryn Roeder,Gerard D. Schellenberg,James S. Sutcliffe,Mark J. Daly,Mark J. Daly +68 more
TL;DR: Results from de novo events and a large parallel case–control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors and support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold.
Journal ArticleDOI
De Novo Gene Disruptions in Children on the Autistic Spectrum
Ivan Iossifov,Michael Ronemus,Dan Levy,Zihua Wang,Inessa Hakker,Julie Rosenbaum,Boris Yamrom,Yoon-ha Lee,Giuseppe Narzisi,Anthony Leotta,Jude Kendall,Ewa A. Grabowska,Beicong Ma,Steven Marks,Linda Rodgers,Asya Stepansky,Jennifer Troge,Peter Andrews,Mitchell A. Bekritsky,Kith Pradhan,Elena Ghiban,Melissa Kramer,Jennifer Parla,Ryan Demeter,Lucinda Fulton,Robert S. Fulton,Vincent Magrini,Kenny Ye,Jennifer C. Darnell,Robert B. Darnell,Robert B. Darnell,Elaine R. Mardis,Richard K. Wilson,Michael C. Schatz,Richard W. McCombie,Michael Wigler +35 more
TL;DR: Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveals de novo small indels and point substitutions, which suggest FMRP-associated genes are especially dosage-sensitive targets of cognitive disorders.
Related Papers (5)
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders
Sarah E Soden,Sarah E Soden,Carol J Saunders,Laurel K. Willig,Laurel K. Willig,Emily G. Farrow,Laurie D. Smith,Laurie D. Smith,Josh E Petrikin,Josh E Petrikin,Jean Baptiste LePichon,Jean Baptiste LePichon,Neil A. Miller,Isabelle Thiffault,Darrell L. Dinwiddie,Greyson P Twist,Aaron Noll,Bryce A. Heese,Lee Zellmer,Andrea M. Atherton,Andrea M. Atherton,Ahmed Abdelmoity,Nicole P. Safina,Sarah S. Nyp,Britton Zuccarelli,Ingrid A. Larson,Ann C. Modrcin,Suzanne Herd,Mitchell Creed,Zhaohui Ye,Xuan Yuan,Robert A. Brodsky,Stephen F. Kingsmore +32 more