Blended phenotype of AP4E1 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15

Hiroaki Murakami, Tomoko Uehara, Yoshinori Tsurusaki, Yumi Enomoto, Yukiko Kuroda, Noriko Aida, Kenjiro Kosaki, Kenji Kurosawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Atypical phenotype of an imprinting disease can develop with a recessive homozygous variant due to uniparental isodisomy. We present a girl with severe intellectual disability, developmental delay, distinctive facial features, and other neuropsychiatric features. Trio whole exome sequencing revealed a novel homozygous frameshift variant in AP4E1 [NM_007347.5:c.2412dupT:p.(Gly805Trpfs*8)] and uniparental isodisomy of chromosome 15 [iUPD(15)]. Single nucleotide polymorphism mapping analysis of exome data showed that the homozygous AP4E1 variant was derived from her heterozygous carrier father and unmasked by paternal iUPD(15). Brain magnetic resonance imaging confirmed the brain abnormalities characteristic of AP4 deficiency including the dilated ventricles and hypointensity in the globus pallidus in susceptibility-weighted imaging. This is the first case report of a combination of AP4E1 deficiency and Angelman syndrome. Our patient indicates that whole exome sequencing could uncover an atypical phenotype caused by multiple genetic factors including the uniparental isodisomy.

Original languageEnglish
Pages (from-to)289-292
Number of pages4
JournalBrain and Development
Issue number3
Publication statusPublished - 2020 Mar


  • AP4E1
  • Angelman syndrome
  • Blended phenotype
  • The neurodegeneration with brain iron accumulation (NBIA)
  • Uniparental isodisomy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology


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