A novel missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria and cleft palate

Koji Kato, Fuyuki Miya, Ikumi Hori, Daisuke Ieda, Kei Ohashi, Yutaka Negishi, Ayako Hattori, Nobuhiko Okamoto, Mitsuhiro Kato, Tatsuhiko Tsunoda, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki, Shinji Saitoh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We identified a novel de novo heterozygous missense mutation in the NEDD4L gene (NM-015277: c.2617G>A; p.Glu873Lys) through whole-exome sequencing in a 3-year-old girl showing severe global developmental delay, infantile spasms, cleft palate, periventricular nodular heterotopia and polymicrogyria. Mutations in the HECT domain of NEDD4L have been reported in patients with a neurodevelopmental disorder along with similar brain malformations. All patients reported with NEDD4L HECT domain mutations showed periventricular nodular heterotopia, and most had seizures, cortex anomalies, cleft palate and syndactyly. The unique constellation of clinical features in patients with NEDD4L mutations might help clinically distinguish them from patients with other genetic mutations including FLNA, which is a well-known causative gene of periventricular nodular heterotopia. Although mutations in the HECT domain of NEDD4L that lead to AKT-mTOR pathway deregulation in forced expression system were reported, our western blot analysis did not show an increased level of AKT-mTOR activity in lymphoblastoid cell lines (LCLs) derived from the patient. In contrast to the forced overexpression system, AKT-mTOR pathway deregulation in LCLs derived from our patient seems to be subtle.

Original languageEnglish
Pages (from-to)861-863
Number of pages3
JournalJournal of Human Genetics
Volume62
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'A novel missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria and cleft palate'. Together they form a unique fingerprint.

  • Cite this

    Kato, K., Miya, F., Hori, I., Ieda, D., Ohashi, K., Negishi, Y., Hattori, A., Okamoto, N., Kato, M., Tsunoda, T., Yamasaki, M., Kanemura, Y., Kosaki, K., & Saitoh, S. (2017). A novel missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria and cleft palate. Journal of Human Genetics, 62(9), 861-863. https://doi.org/10.1038/jhg.2017.53