Variable Phenotypes of Epilepsy, Intellectual Disability, and Schizophrenia Caused by 12p13.33-p13.32 Terminal Microdeletion in a Korean Family: A Case Report and Literature Review

• Published in: Genes Vol. 12; no. 7; p. 1001
• Main Authors: Han, Ji Yoon, Park, Joonhong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-06-2021; MDPI
• Subjects: Calcium Channels, L-Type - genetics; Case Report; Case reports; Child; Chromosome Deletion; Chromosomes, Human, Pair 12 - genetics; Chromosomes, Human, Pair 12 - physiology; Congenital diseases; Convulsions & seizures; Copy number; Epilepsy; Epilepsy - genetics; Epilepsy - pathology; Female; Genomes; Genomics; Humans; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - pathology; Laboratories; Life span; Literature reviews; Mental disorders; Monosomy; Pedigree; Phenotype; Phenotypes; Phenotyping; Retinoblastoma-Binding Protein 2 - genetics; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Software; United States > US; epilepsy; KDM5A gene; variable phenotypes; chromosomal microarray; exome sequencing; 12p13.33 microdeletion; schizophrenia; CACNA1C gene; intellectual disability
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12071001

A simultaneous analysis of nucleotide changes and copy number variations (CNVs) based on exome sequencing data was demonstrated as a potential new first-tier diagnosis strategy for rare neuropsychiatric disorders. In this report, using depth-of-coverage analysis from exome sequencing data, we described variable phenotypes of epilepsy, intellectual disability (ID), and schizophrenia caused by 12p13.33-p13.32 terminal microdeletion in a Korean family. We hypothesized that
and
genes of the six candidate genes located in this region were the best candidates for explaining epilepsy, ID, and schizophrenia and may be responsible for clinical features reported in cases with monosomy of the 12p13.33 subtelomeric region. On the background of microdeletion syndrome, which was described in clinical cases with mild, moderate, and severe neurodevelopmental manifestations as well as impairments, the clinician may determine whether the patient will end up with a more severe or milder end-phenotype, which in turn determines disease prognosis. In our case, the 12p13.33-p13.32 terminal microdeletion may explain the variable expressivity in the same family. However, further comprehensive studies with larger cohorts focusing on careful phenotyping across the lifespan are required to clearly elucidate the possible contribution of genetic modifiers and the environmental influence on the expressivity of 12p13.33 microdeletion and associated characteristics.