1. Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.
- Author
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Miyamoto S, Kato M, Hiraide T, Shiohama T, Goto T, Hojo A, Ebata A, Suzuki M, Kobayashi K, Chong PF, Kira R, Matsushita HB, Ikeda H, Hoshino K, Matsufuji M, Moriyama N, Furuyama M, Yamamoto T, Nakashima M, and Saitsu H
- 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
- 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., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
- Published
- 2021
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