Modeling the Human Neuronal Phenotype of the Schizophrenia-Associated 3q29 deletion

精神分裂症相关 3q29 缺失的人类神经元表型建模

• 批准号: 10540501
• 负责人: Jennifer Gladys Mulle
• 金额: $ 31.31万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-07 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540501
• 关键词: Modeling; Human; Neuronal; Phenotype; Schizophrenia

Project Summary/Abstract 3q29 deletion syndrome is caused by a recurrent typically de novo 1.6 Mb heterozygous deletion and is associated with a range of neuropsychiatric phenotypes, including mild to moderate intellectual disability, autism, anxiety, and a 40-fold increased risk for schizophrenia. Although the 3q29 deletion is rare (~1 in 30,000 births), its high risk for neuropsychiatric phenotypes coupled with its relatively low complexity (22 genes in the deletion interval) make it ideal for molecular dissection. Investigating the neuronal phenotype caused by 3q29 deletion may reveal a core neurodevelopmental process that is disrupted in schizophrenia, autism, and/or intellectual disability. We propose to assess deletion carriers for behavioral traits along 4 dimensions: cognitive ability, anxiety, autism spectrum, and presence of psychosis or prodromal features. We will also collect blood samples from deletion carriers and related controls and bank these materials in the Rutgers University Cell and DNA Repository (RUCDR) for use by the research community. Finally, we will model the human neuronal phenotype using iPSC lines derived from deletion carriers who have psychosis. This will be the first human neuronal model of the 3q29 deletion. Understanding the specific biological processes disrupted by deletion of the 22 genes in this interval may provide a molecular window into key neurodevelopmental processes relevant to neuropsychiatric phenotypes. All phenotypic data, molecular data, and cell lines will be rapidly shared through NDAR, dbGaP (dbgap.ncbi.nlm.nih.gov) and the NIMH Repository and Genomics Resource (nimhgenetics.org).

项目总结/文摘

项目成果

Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome.

• DOI: 10.1186/s13229-022-00533-2
• 发表时间: 2022-12-24
• 期刊: Molecular autism
• 影响因子: 6.2

Caregiver Perspectives on a Child's Diagnosis of 3q29 Deletion: "We Can't Just Wish This Thing Away".

• DOI: 10.1097/dbp.0000000000000977
• 发表时间: 2022-02-01
• 期刊: Journal of developmental and behavioral pediatrics : JDBP
• 作者: Glassford MR;Purcell RH;Pass S;Murphy MM;Bassell GJ;Mulle JG;Emory 3q29 Project,*
• 通讯作者: Emory 3q29 Project,*

Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care.

• DOI: 10.1038/s41436-020-01053-1
• 发表时间: 2021-05
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Sanchez Russo R;Gambello MJ;Murphy MM;Aberizk K;Black E;Burrell TL;Carlock G;Cubells JF;Epstein MT;Espana R;Goines K;Guest RM;Klaiman C;Koh S;Leslie EJ;Li L;Novacek DM;Saulnier CA;Sefik E;Shultz S;Walker E;White SP;Emory 3q29 Project;Mulle JG
• 通讯作者: Mulle JG

Adaptive behavior deficits in individuals with 3q29 deletion syndrome.

3q29 缺失综合征个体的适应性行为缺陷。

• DOI: 10.1101/2023.03.31.23288022
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Pollak,RebeccaM;Burrell,TLindsey;Cubells,JosephF;Klaiman,Cheryl;Murphy,MelissaM;Saulnier,CelineA;Walker,ElaineF;White,StormiPulver;Mulle,JenniferG
• 通讯作者: Mulle,JenniferG

Visual-Motor Integration Deficits in 3q29 Deletion Syndrome.

3q29 缺失综合征中的视觉运动整合缺陷。

• DOI: 10.1007/s10803-023-06034-2
• 发表时间: 2023
• 期刊: Journal of autism and developmental disorders
• 影响因子: 3.9
• 作者: Pollak,RebeccaM;Burrell,TLindsey;Cubells,JosephF;Klaiman,Cheryl;Murphy,MelissaM;Saulnier,CelineA;Walker,ElaineF;White,StormiPulver;Mulle,JenniferG
• 通讯作者: Mulle,JenniferG