A recurrent single-exon deletion in TBCKmight be under-recognizedin patients with infantile hypotonia and psychomotor delay.

Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, whiledetection of single-exon CNVsremainschallenging.A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individualswith homozygous single-exon deletions of TBCK(exon23, 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 analyzedsingle nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon23 TBCK deletions.A fifth individual was diagnosed with the TBCK-related disorder due to a heterozygous exon23 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, HispanicAmerican and African American, with only one family reporting consanguinity.RT-PCR revealedtwoout-of-frame transcripts related to the exon23 deletion.Our results highlight the importance of identifying single-exon deletionsin clinical ES, especially for genes carrying recurrent deletions. For patients with early-onset hypotonia and psychomotor delay, this single-exon TBCKdeletion might be under-recognized due to technical limitations of ES. This article is protected by copyright. All rights reserved.