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A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.
Dai, Hongzheng; Zhu, Wenmiao; Yuan, Bo; Walley, Nicole; Schoch, Kelly; Jiang, Yong-Hui; Phillips, John A; Jones, Melissa S; Liu, Pengfei; Murdock, David R; Burrage, Lindsay C; Lee, Brendan; Rosenfeld, Jill A; Xiao, Rui.
Afiliação
  • Dai H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
  • Zhu W; Baylor Genetics, Houston, Texas, USA.
  • Yuan B; Baylor Genetics, Houston, Texas, USA.
  • Walley N; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
  • Schoch K; Baylor Genetics, Houston, Texas, USA.
  • Jiang YH; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
  • Phillips JA; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
  • Jones MS; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
  • Liu P; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
  • Murdock DR; Department of Medical Genetics and Genomic Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Burrage LC; Houston Area Pediatric Neurology, Katy, Texas, USA.
  • Lee B; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
  • Rosenfeld JA; Baylor Genetics, Houston, Texas, USA.
  • Xiao R; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Hum Mutat ; 43(12): 1816-1823, 2022 12.
Article em En | MEDLINE | ID: mdl-36317458
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Hipotonia Muscular / Doenças Musculares Tipo de estudo: Risk_factors_studies Limite: Humans / Infant Idioma: En Revista: Hum Mutat Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Hipotonia Muscular / Doenças Musculares Tipo de estudo: Risk_factors_studies Limite: Humans / Infant Idioma: En Revista: Hum Mutat Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos