Language
English
Publication Date
12-1-2022
Journal
Human Mutation
DOI
10.1002/humu.24497
PMID
36317458
PMCID
PMC9772143
PubMedCentral® Posted Date
12-1-2023
PubMedCentral® Full Text Version
Author MSS
Abstract
Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed with the TBCK-related disorder due to a heterozygous exon 23 deletion in trans with a c.1860+1G>A (NM_001163435.2) pathogenic variant, and three additional heterozygous carriers were identified. Affected individuals and carriers were from diverse ethnicities including European Caucasian, South Asian, Middle Eastern, Hispanic American and African American, with only one family reporting consanguinity. RT-PCR revealed two out-of-frame transcripts related to the exon 23 deletion. Our results highlight the importance of identifying single-exon deletions in clinical ES, especially for genes carrying recurrent deletions. For patients with early-onset hypotonia and psychomotor delay, this single-exon TBCK deletion might be under-recognized due to technical limitations of ES.
Keywords
Humans, DNA Copy Number Variations, Exome, Exome Sequencing, Exons, Muscle Hypotonia, Muscular Diseases, Protein Serine-Threonine Kinases, Retrospective Studies, Infant, TBCK, single-exon deletion, exome sequencing, diagnostic testing, recurrent variant
Published Open-Access
yes
Recommended Citation
Dai, Hongzheng; Zhu, Wenmiao; Yuan, Bo; et al., "A Recurrent Single-Exon Deletion in TBCK Might Be Under-Recognized in Patients With Infantile Hypotonia and Psychomotor Delay" (2022). Faculty and Staff Publications. 5002.
https://digitalcommons.library.tmc.edu/baylor_docs/5002
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