A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology

Nobuhiko Okamoto, Yuki Tsuchiya, Fuyuki Miya, Tatsuhiko Tsunoda, Kumiko Yamashita, Keith A. Boroevich, Mitsuhiro Kato, Shinji Saitoh, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki, Daiju Kitagawa

研究成果: Article査読

4 被引用数 (Scopus)

抄録

Intellectual disability (ID) is one of neurodevelopmental disorders characterized by serious defects in both intelligence and adaptive behavior. Although it has been suggested that genetic aberrations associated with the process of cell division underlie ID, the cytological evidence for mitotic defects in actual patient's cells is rarely reported. Here, we report a novel mutation in the STARD9 (also known as KIF16A) gene found in a patient with severe ID, characteristic features, epilepsy, acquired microcephaly, and blindness. Using whole-exome sequence analysis, we sequenced potential candidate genes in the patient. We identified a homozygous single-nucleotide deletion creating a premature stop codon in the STARD9 gene. STARD9 encodes a 4,700 amino acid protein belonging to the kinesin superfamily. Depletion of STARD9 or overexpression of C-terminally truncated STARD9 mutants were known to induce spindle assembly defects in human culture cells. To determine cytological features in the patient cells, we isolated lymphoblast cells from the patient, and performed immunofluorescence analysis. Remarkably, mitotic defects, including multipolar spindle formation, fragmentation of pericentriolar materials and centrosome amplification, were observed in the cells. Taken together, our findings raise the possibility that controlled expression of full-length STARD9 is necessary for proper spindle assembly in cell division during human development. We propose that mutations in STARD9 result in abnormal spindle morphology and cause a novel genetic syndrome with ID.

本文言語English
ページ(範囲)2690-2696
ページ数7
ジャーナルAmerican Journal of Medical Genetics, Part A
173
10
DOI
出版ステータスPublished - 2017 10月

ASJC Scopus subject areas

  • 遺伝学
  • 遺伝学(臨床)

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