Novel compound heterozygous variants in PLK4 identified in a patient with autosomal recessive microcephaly and chorioretinopathy

Makiko Tsutsumi, Setsuri Yokoi, Fuyuki Miya, Masafumi Miyata, Mitsuhiro Kato, Nobuhiko Okamoto, Tatsuhiko Tsunoda, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki, Shinji Saitoh, Hiroki Kurahashi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

It has been well documented that variants in genes encoding centrosomal proteins cause primary autosomal recessive microcephaly, although the association between centrosomal defects and the etiology of microcephaly syndromes is not fully understood. Polo-like kinase 4 (PLK4) is one of the centrosomal proteins required for centriole duplication. We here describe a patient with microcephaly and chorioretinopathy that harbors compound heterozygous missense variants, c.[442A>G]; [2336G>A], in the PLK4 gene. One of these variants, c.442A>G (p.(M148V)), resides in the kinase domain, and the other, c.2336G>A (p.(C779Y)), in the polo-box domain. Aberrant spindle formation was observed in a LCL derived from this patient. Overexpression experiments of the variant PLK4 proteins demonstrated that the p.(C779Y) but not the p.(M148V) had lost centriole overduplication ability. The altered mobility pattern of both variant proteins on a western blot further suggested alterations in post-translation modification. Our data lend support to the hypothesis that impaired centriole duplication caused by PLK4 variants may be involved in the etiology of microcephaly disorder.

Original languageEnglish
Pages (from-to)1702-1706
Number of pages5
JournalEuropean Journal of Human Genetics
Volume24
Issue number12
DOIs
Publication statusPublished - 01-12-2016

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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