MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1016/j.ajhg.2021.01.015

Медицинская библиотека · American journal of human genetics · 2021

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.

Radio Francesca Clementina, Pang Kaifang, Ciolfi Andrea, Levy Michael A, Hernández-García Andrés, Pedace Lucia, Pantaleoni Francesca, Liu Zhandong, de Boer Elke, Jackson Adam, Bruselles Alessandro, McConkey Haley, Stellacci Emilia, Lo Cicero Stefania, Motta Marialetizia, Carrozzo Rosalba, Dentici Maria Lisa, McWalter Kirsty, Desai Megha, Monaghan Kristin G, Telegrafi Aida, Philippe Christophe, Vitobello Antonio, Au Margaret, Grand Katheryn, Sanchez-Lara Pedro A, Baez Joanne, Lindstrom Kristin, Kulch Peggy, Sebastian Jessica, Madan-Khetarpal Suneeta, Roadhouse Chelsea, MacKenzie Jennifer J, Monteleone Berrin, Saunders Carol J, Jean Cuevas July K, Cross Laura, Zhou Dihong, Hartley Taila, Sawyer Sarah L, Monteiro Fabíola Paoli, Secches Tania Vertemati, Kok Fernando, Schultz-Rogers Laura E, Macke Erica L, Morava Eva, Klee Eric W, Kemppainen Jennifer, Iascone Maria, Selicorni Angelo, Tenconi Romano, Amor David J, Pais Lynn, Gallacher Lyndon, Turnpenny Peter D, Stals Karen, Ellard Sian, Cabet Sara, Lesca Gaetan, Pascal Joset, Steindl Katharina, Ravid Sarit, Weiss Karin, Castle Alison M R, Carter Melissa T, Kalsner Louisa, de Vries Bert B A, van Bon Bregje W, Wevers Marijke R, Pfundt Rolph, Stegmann Alexander P A, Kerr Bronwyn, Kingston Helen M, Chandler Kate E, Sheehan Willow, Elias Abdallah F, Shinde Deepali N, Towne Meghan C, Robin Nathaniel H, Goodloe Dana, Vanderver Adeline, Sherbini Omar, Bluske Krista, Hagelstrom R Tanner, Zanus Caterina, Faletra Flavio, Musante Luciana, Kurtz-Nelson Evangeline C, Earl Rachel K, Anderlid Britt-Marie, Morin Gilles, van Slegtenhorst Marjon, Diderich Karin E M, Brooks Alice S, Gribnau Joost, Boers Ruben G, Finestra Teresa Robert, Carter Lauren B, Rauch Anita, Gasparini Paolo, Boycott Kym M, Barakat Tahsin Stefan, Graham John M, Faivre Laurence, Banka Siddharth, Wang Tianyun, Eichler Evan E, Priolo Manuela, Dallapiccola Bruno, Vissers Lisenka E L M, Sadikovic Bekim, Scott Daryl A, Holder Jimmy Lloyd, Tartaglia Marco

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.

Для цитирования: Radio Francesca Clementina, Pang Kaifang, Ciolfi Andrea, Levy Michael A, Hernández-García Andrés, Pedace Lucia, Pantaleoni Francesca, Liu Zhandong, de Boer Elke, Jackson Adam, Bruselles Alessandro, McConkey Haley, Stellacci Emilia, Lo Cicero Stefania, Motta Marialetizia, Carrozzo Rosalba, Dentici Maria Lisa, McWalter Kirsty, Desai Megha, Monaghan Kristin G, Telegrafi Aida, Philippe Christophe, Vitobello Antonio, Au Margaret, Grand Katheryn, Sanchez-Lara Pedro A, Baez Joanne, Lindstrom Kristin, Kulch Peggy, Sebastian Jessica, Madan-Khetarpal Suneeta, Roadhouse Chelsea, MacKenzie Jennifer J, Monteleone Berrin, Saunders Carol J, Jean Cuevas July K, Cross Laura, Zhou Dihong, Hartley Taila, Sawyer Sarah L, Monteiro Fabíola Paoli, Secches Tania Vertemati, Kok Fernando, Schultz-Rogers Laura E, Macke Erica L, Morava Eva, Klee Eric W, Kemppainen Jennifer, Iascone Maria, Selicorni Angelo, Tenconi Romano, Amor David J, Pais Lynn, Gallacher Lyndon, Turnpenny Peter D, Stals Karen, Ellard Sian, Cabet Sara, Lesca Gaetan, Pascal Joset, Steindl Katharina, Ravid Sarit, Weiss Karin, Castle Alison M R, Carter Melissa T, Kalsner Louisa, de Vries Bert B A, van Bon Bregje W, Wevers Marijke R, Pfundt Rolph, Stegmann Alexander P A, Kerr Bronwyn, Kingston Helen M, Chandler Kate E, Sheehan Willow, Elias Abdallah F, Shinde Deepali N, Towne Meghan C, Robin Nathaniel H, Goodloe Dana, Vanderver Adeline, Sherbini Omar, Bluske Krista, Hagelstrom R Tanner, Zanus Caterina, Faletra Flavio, Musante Luciana, Kurtz-Nelson Evangeline C, Earl Rachel K, Anderlid Britt-Marie, Morin Gilles, van Slegtenhorst Marjon, Diderich Karin E M, Brooks Alice S, Gribnau Joost, Boers Ruben G, Finestra Teresa Robert, Carter Lauren B, Rauch Anita, Gasparini Paolo, Boycott Kym M, Barakat Tahsin Stefan, Graham John M, Faivre Laurence, Banka Siddharth, Wang Tianyun, Eichler Evan E, Priolo Manuela, Dallapiccola Bruno, Vissers Lisenka E L M, Sadikovic Bekim, Scott Daryl A, Holder Jimmy Lloyd, Tartaglia Marco. SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.. American journal of human genetics. 2021. DOI: 10.1016/j.ajhg.2021.01.015.

Предметные рубрики MeSH

AdolescentAutism Spectrum DisorderChildChild, PreschoolChromosome DeletionChromosome DisordersChromosomes, Human, Pair 1Chromosomes, Human, XDNA MethylationDNA-Binding ProteinsEpigenesis, GeneticFemaleHaploinsufficiencyHumansIntellectual DisabilityNeurodevelopmental DisordersPhenotypeRNA-Binding ProteinsYoung Adult
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.