A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay

Bettina E. Mucha, Siddhart Banka, Norbert Fonya Ajeawung, Sirinart Molidperee, Gary G. Chen, Mary Kay Koenig, Rhamat B. Adejumo, Marianne Till, Michael Harbord, Renee Perrier, Emmanuelle Lemyre, Renee Myriam Boucher, Brian G. Skotko, Jessica L. Waxler, Mary Ann Thomas, Jennelle C. Hodge, Jozef Gecz, Jillian Nicholl, Lesley McGregor, Tobias LindenSanjay M. Sisodiya, Damien Sanlaville, Sau W. Cheung, Carl Ernst, Philippe M. Campeau

Research output: Contribution to journalArticle

3 Citations (Scopus)


Purpose: Contiguous gene deletions are known to cause several neurodevelopmental syndromes, many of which are caused by recurrent events on chromosome 16. However, chromosomal microarray studies (CMA) still yield copy-number variants (CNVs) of unknown clinical significance. We sought to characterize eight individuals with overlapping 205-kb to 504-kb 16p13.3 microdeletions that are distinct from previously published deletion syndromes. Methods: Clinical information on the patients and bioinformatic scores for the deleted genes were analyzed. Results: All individuals in our cohort displayed developmental delay, intellectual disability, and various forms of seizures. Six individuals were microcephalic and two had strabismus. The deletion was absent in all 13 parents who were available for testing. The area of overlap encompasses seven genes including TBC1D24, ATP6V0C, and PDPK1 (also known as PDK1). Bi-allelic TBC1D24 pathogenic variants are known to cause nonsyndromic deafness, epileptic disorders, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures). Sanger sequencing of the nondeleted TBC1D24 allele did not yield any additional pathogenic variants. Conclusions: We propose that 16p13.3 microdeletions resulting in simultaneous haploinsufficiencies of TBC1D24, ATP6V0C, and PDPK1 cause a novel rare contiguous gene deletion syndrome of microcephaly, developmental delay, intellectual disability, and epilepsy.

Original languageEnglish
Pages (from-to)1058-1064
Number of pages7
JournalGenetics in Medicine
Issue number5
Publication statusPublished - 1 May 2019


  • 16p13.3
  • Epilepsy
  • Microcephaly
  • Microdeletion
  • TBC1D24

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Mucha, B. E., Banka, S., Ajeawung, N. F., Molidperee, S., Chen, G. G., Koenig, M. K., ... Campeau, P. M. (2019). A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay. Genetics in Medicine, 21(5), 1058-1064. https://doi.org/10.1038/s41436-018-0290-3