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Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.
- Source :
-
Journal of human genetics [J Hum Genet] 2021 Nov; Vol. 66 (11), pp. 1061-1068. Date of Electronic Publication: 2021 May 06. - Publication Year :
- 2021
-
Abstract
- Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs.<br /> (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
- Subjects :
- Adolescent
Adult
Agenesis of Corpus Callosum complications
Agenesis of Corpus Callosum genetics
Agenesis of Corpus Callosum pathology
Brain pathology
Brain Diseases complications
Brain Diseases diagnosis
Brain Diseases genetics
Brain Diseases pathology
Child
Child, Preschool
Congenital Abnormalities genetics
Congenital Abnormalities pathology
Corpus Callosum diagnostic imaging
Corpus Callosum pathology
DNA Copy Number Variations genetics
Female
Humans
Intellectual Disability complications
Intellectual Disability diagnosis
Intellectual Disability genetics
Intellectual Disability pathology
Japan
Lateral Ventricles abnormalities
Lateral Ventricles pathology
Male
Motor Disorders complications
Motor Disorders diagnosis
Motor Disorders genetics
Motor Disorders pathology
Mutation genetics
Nervous System Malformations complications
Nervous System Malformations genetics
Nervous System Malformations pathology
Phenotype
Exome Sequencing
Young Adult
Agenesis of Corpus Callosum diagnosis
Brain diagnostic imaging
Congenital Abnormalities diagnosis
Nervous System Malformations diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 66
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 33958710
- Full Text :
- https://doi.org/10.1038/s10038-021-00932-y