PDF(Pubmed)
Abstract：
UNASSIGNED: Intellectual disability (ID) is a lifelong disability that affects an individual‧s learning capacity and adaptive behavior. Such individuals depend on their families for day-to-day survival and pose a significant challenge to the healthcare system, especially in developing countries. ID is a heterogeneous condition, and genetic studies are essential to unravel the underlying cellular pathway for brain development and functioning.
UNASSIGNED: Here we studied a female index patient, born to a consanguineous Pakistani couple, showing clinical symptoms of ID, ataxia, hypotonia, developmental delay, seizures, speech abnormality, and aggressive behavior. Whole exome sequencing (WES) coupled with Sanger sequencing was performed for molecular diagnosis. Further, 3D protein modeling was performed to see the effect of variant on protein structure.
UNASSIGNED: WES identified a novel homozygous missense variant (c.178T>C; p.Tyr60His) in the ANK3 gene. In silico analysis and 3-dimensional (3D) protein modeling supports the deleterious impact of this variant on the encoding protein, which compromises the protein‧s overall structure and function.
UNASSIGNED: Our finding supports the clinical and genetic diversity of the ANK3 gene as a plausible candidate gene for ID syndrome. Intelligence is a complex polygenic human trait, and understanding molecular and biological pathways involved in learning and memory can solve the complex puzzle of how cognition develops. Intellectual disability (ID) is defined as a deficit in an individual‧s learning and adaptive behavior at an early age of onset [American Psychiatric Association, 2013]. It is one of the major medical, and cognitive disorders with a prevalence of 1-3% in the population worldwide [Leonard and Wen, 2002]. ID often exists with other disabling mental conditions such as autism, attention deficit hyperactivity disorder, epilepsy, schizophrenia, bipolar disorder, or depression. Almost half of the cases appear to have a genetic explanation that ranges from cytogenetically visible abnormalities to monogenic defects [Flint, 2001; Ropers, 2010; Tucker-Drob et al., 2013]. Intellectual disability is a genetically heterogeneous condition, and more than 700 genes have been identified to cause ID alone or as a part of the syndrome. Research in X-linked ID has identified more than 100 disease-causing genes on the X chromosome that play a role in cognition; however, research into autosomal causes of ID is still ongoing [Vissers et al., 2016].
UNASSIGNED: Here we studied a female index patient, born to a consanguineous Pakistani couple, showing clinical symptoms of ID, ataxia, hypotonia, developmental delay, seizures, speech abnormality, and aggressive behavior. Whole exome sequencing (WES) coupled with Sanger sequencing was performed for molecular diagnosis. Further, 3D protein modeling was performed to see the effect of variant on protein structure.
UNASSIGNED: WES identified a novel homozygous missense variant (c.178T>C; p.Tyr60His) in the ANK3 gene. In silico analysis and 3-dimensional (3D) protein modeling supports the deleterious impact of this variant on the encoding protein, which compromises the protein‧s overall structure and function.
UNASSIGNED: Our finding supports the clinical and genetic diversity of the ANK3 gene as a plausible candidate gene for ID syndrome. Intelligence is a complex polygenic human trait, and understanding molecular and biological pathways involved in learning and memory can solve the complex puzzle of how cognition develops. Intellectual disability (ID) is defined as a deficit in an individual‧s learning and adaptive behavior at an early age of onset [American Psychiatric Association, 2013]. It is one of the major medical, and cognitive disorders with a prevalence of 1-3% in the population worldwide [Leonard and Wen, 2002]. ID often exists with other disabling mental conditions such as autism, attention deficit hyperactivity disorder, epilepsy, schizophrenia, bipolar disorder, or depression. Almost half of the cases appear to have a genetic explanation that ranges from cytogenetically visible abnormalities to monogenic defects [Flint, 2001; Ropers, 2010; Tucker-Drob et al., 2013]. Intellectual disability is a genetically heterogeneous condition, and more than 700 genes have been identified to cause ID alone or as a part of the syndrome. Research in X-linked ID has identified more than 100 disease-causing genes on the X chromosome that play a role in cognition; however, research into autosomal causes of ID is still ongoing [Vissers et al., 2016].
摘要：
未经评估：智力残疾（ID）是一种影响个体学习能力和适应行为的终身残疾。这些人依靠家人维持日常生存，对医疗保健系统构成重大挑战，尤其是在发展中国家。ID是一个异构条件，遗传研究对于解开大脑发育和功能的潜在细胞途径至关重要。
未经评估：在这里，我们研究了一位女性指数患者，出生于一对有血缘关系的巴基斯坦夫妇,显示ID的临床症状，共济失调,低张力,发育迟缓,癫痫发作,言语异常,和攻击性行为。进行全外显子组测序(WES)结合Sanger测序用于分子诊断。Further,进行3D蛋白质建模以观察变体对蛋白质结构的影响。
未经鉴定：WES在ANK3基因中鉴定出一种新的纯合错义变体（c.178T>C；p.Tyr60His）。计算机模拟分析和3维（3D）蛋白质建模支持该变体对编码蛋白质的有害影响，这损害了蛋白质的整体结构和功能。
UNASSIGNED：我们的发现支持ANK3基因的临床和遗传多样性，作为ID综合征的一个似是而非的候选基因。智力是一种复杂的多基因人类特征，理解学习和记忆中涉及的分子和生物学途径可以解决认知如何发展的复杂难题。智力残疾(ID)被定义为个体在发病初期的学习和适应行为的缺陷[美国精神病学协会,2013].它是主要的医学之一，和认知障碍在全球人口中的患病率为1-3%[伦纳德和温，2002].ID通常存在于其他残疾的精神疾病中，如自闭症，注意缺陷多动障碍,癫痫,精神分裂症,双相情感障碍,或抑郁症。几乎一半的病例似乎具有从细胞遗传学可见异常到单基因缺陷的遗传解释[弗林特，2001；Ropers，2010；Tucker-Drob等人。,2013].智力残疾是一种遗传异质性的疾病，已经鉴定出700多个基因单独或作为综合征的一部分引起ID。X连锁ID的研究已经确定了X染色体上100多个在认知中起作用的致病基因；然而，对ID的常染色体病因的研究仍在进行中[Vissers等人。,2016].
未经评估：在这里，我们研究了一位女性指数患者，
未经鉴定：WES在ANK3基因中鉴定出一种新的纯合错义变体（c.178T>C；p.Tyr60His）。
UNASSIGNED：我们的发现支持ANK3基因的临床和遗传多样性，作为ID综合征的一个似是而非的候选基因。
