Biallelic loss of OTUD7A causes severe muscular hypotonia, intellectual disability, and seizures

Hisato Suzuki, Mie Inaba, Mamiko Yamada, Tomoko Uehara, Toshiki Takenouchi, Seiji Mizuno, Kenjiro Kosaki, Motomichi Doi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


The heterozygous deletion of 15q13.3 is a recurrently observed microdeletion syndrome associated with a relatively mild phenotype including learning disability and language impairment. In contrast, the homozygous deletion of 15q13.3 is extremely rare and is associated with a much severer phenotype that includes epileptic encephalopathy, profound intellectual disability, and hypotonia. Which of the genes within the deleted interval is responsible for the more severe features when biallelically deleted is currently unknown. Here, we report a patient with profound hypotonia, severe intellectual disability, and seizures who had biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del, p.(Glu375Aspfs*11). Unexpectedly, both aberrations occurred de novo. Our experiment using Caenorhabditis elegans showed that worms carrying a corresponding homozygous variant in the homolog OTUB-2 exhibited weakened muscle contraction suggestive of aberrant neuromuscular transmission. We concluded that the biallelic complete loss of OTUD7A in humans represents a presumably new autosomal recessive disorder characterized by profound hypotonia, severe intellectual disability, and seizures.

Original languageEnglish
Pages (from-to)1182-1186
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number4
Publication statusPublished - 2021 Apr


  • 15q13.3 microdeletion syndrome
  • CHRNA7
  • OTUD7A

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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