A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities
Background: 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 -re...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402403977X |
| _version_ | 1827294012960145408 |
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| author | Sheng Yi Xianglian Tang Qiang Zhang Yu Liang Jing Huang Shujie Zhang Limei Huang Shang Yi Minpan Huang Zailong Qin Jingsi Luo |
| author_facet | Sheng Yi Xianglian Tang Qiang Zhang Yu Liang Jing Huang Shujie Zhang Limei Huang Shang Yi Minpan Huang Zailong Qin Jingsi Luo |
| author_sort | Sheng Yi |
| collection | DOAJ |
| description | Background: 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. Methods: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene. Results: 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. Conclusions: 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. |
| first_indexed | 2024-04-24T13:48:41Z |
| format | Article |
| id | doaj.art-d1b5d4d383504436a9974227e10905b8 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:48:41Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d1b5d4d383504436a9974227e10905b82024-04-04T05:06:25ZengElsevierHeliyon2405-84402024-03-01106e27946A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformitiesSheng Yi0Xianglian Tang1Qiang Zhang2Yu Liang3Jing Huang4Shujie Zhang5Limei Huang6Shang Yi7Minpan Huang8Zailong Qin9Jingsi Luo10Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Pathology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Obstetrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGenetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Corresponding author. Laboratory of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, China.Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Corresponding author. Laboratory of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, China.Background: 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. Methods: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene. Results: 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. Conclusions: 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.http://www.sciencedirect.com/science/article/pii/S240584402403977XCC2D1AAutism spectrum disorderIntellectual disabilityMotor delayHypotoniaNovel variants |
| spellingShingle | Sheng Yi Xianglian Tang Qiang Zhang Yu Liang Jing Huang Shujie Zhang Limei Huang Shang Yi Minpan Huang Zailong Qin Jingsi Luo A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities Heliyon CC2D1A Autism spectrum disorder Intellectual disability Motor delay Hypotonia Novel variants |
| title | A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities |
| title_full | A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities |
| title_fullStr | A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities |
| title_full_unstemmed | A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities |
| title_short | A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities |
| title_sort | nonsense cc2d1a variant is associated with congenital anomalies motor delay hypotonia and slight deformities |
| topic | CC2D1A Autism spectrum disorder Intellectual disability Motor delay Hypotonia Novel variants |
| url | http://www.sciencedirect.com/science/article/pii/S240584402403977X |
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