PDF(Pubmed)
Abstract：
UNASSIGNED: Autosomal recessive intellectual developmental disorder-3 is caused by homozygous or compound heterozygous mutations in the CC2D1A gene. The disorder is characterized by intellectual disability (ID) and autism spectrum disorder (ASD). To date, 39 patients from 17 families with CC2D1A -related disorders have been reported worldwide, in whom only six pathogenic or likely pathogenic loss-of-function variants and three variants of uncertain significance (VUS) in the CC2D1A gene have been identified in these patients.
UNASSIGNED: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene.
UNASSIGNED: The patient presented with severe ID and ASD, speech impairment, motor delay, hypotonia, slight facial anomalies, and finger deformities. Threatened abortion and abnormal fetal movements occurred during pregnancy with the proband but not his older healthy sister. WES analysis identified a homozygous nonsense variant, c.736C > T (p.Gln246Ter), in the CC2D1A gene. In addition, six novel likely pathogenic CC2D1A variants were identified by a retrospective review of the in-house database.
UNASSIGNED: This study expands the genetic and clinical spectra of CC2D1A-associated disorders, and may aid in increasing awareness of this rare condition. Our findings have provided new insights into the clinical heterogeneity of the disease and further phenotype-genotype correlation, which could help to offer scope for more accurate genetic testing and counseling to affected families.
UNASSIGNED: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene.
UNASSIGNED: The patient presented with severe ID and ASD, speech impairment, motor delay, hypotonia, slight facial anomalies, and finger deformities. Threatened abortion and abnormal fetal movements occurred during pregnancy with the proband but not his older healthy sister. WES analysis identified a homozygous nonsense variant, c.736C > T (p.Gln246Ter), in the CC2D1A gene. In addition, six novel likely pathogenic CC2D1A variants were identified by a retrospective review of the in-house database.
UNASSIGNED: This study expands the genetic and clinical spectra of CC2D1A-associated disorders, and may aid in increasing awareness of this rare condition. Our findings have provided new insights into the clinical heterogeneity of the disease and further phenotype-genotype correlation, which could help to offer scope for more accurate genetic testing and counseling to affected families.
摘要：
■常染色体隐性智力发育障碍-3是由CC2D1A基因中的纯合或复合杂合突变引起的。该障碍的特征在于智力障碍(ID)和自闭症谱系障碍(ASD)。迄今为止,在全球范围内，有来自17个CC2D1A相关疾病家庭的39名患者被报道，在这些患者中，仅在CC2D1A基因中发现了6种致病性或可能的致病性功能丧失变体和3种意义不确定的变体（VUS）。
■我们描述了一个来自非近亲中国家庭的ID患者，并使用全外显子组测序（WES）来鉴定致病基因。
■患者表现为严重的ID和ASD，言语障碍,电机延迟,低张力,轻微的面部异常,手指畸形。先证者在怀孕期间发生了先证者的先兆流产和异常的胎儿运动，但他的健康姐姐却没有。WES分析确定了纯合无义变体，c.736C>T（p。Gln246Ter),在CC2D1A基因中。此外,通过对内部数据库的回顾性审查,发现了6种新的可能致病的CC2D1A变异体.
■这项研究扩展了CC2D1A相关疾病的遗传和临床范围，并可能有助于提高人们对这种罕见疾病的认识。我们的发现为疾病的临床异质性和进一步的表型-基因型相关性提供了新的见解。这可能有助于为受影响的家庭提供更准确的基因检测和咨询。
■我们描述了一个来自非近亲中国家庭的ID患者，并使用全外显子组测序（WES）来鉴定致病基因。
■患者表现为严重的ID和ASD，言语障碍,电机延迟,低张力,轻微的面部异常,手指畸形。先证者在怀孕期间发生了先证者的先兆流产和异常的胎儿运动，但他的健康姐姐却没有。WES分析确定了纯合无义变体，c.736C>T（p。Gln246Ter),在CC2D1A基因中。此外,通过对内部数据库的回顾性审查,发现了6种新的可能致病的CC2D1A变异体.
■这项研究扩展了CC2D1A相关疾病的遗传和临床范围，并可能有助于提高人们对这种罕见疾病的认识。我们的发现为疾病的临床异质性和进一步的表型-基因型相关性提供了新的见解。这可能有助于为受影响的家庭提供更准确的基因检测和咨询。
