De novo POGZ mutations are associated with neurodevelopmental disorders and microcephaly

Yizhou Ye; Megan T Cho; Kyle Retterer; Nora Alexander; Tawfeg Ben-Omran; Mariam Al-Mureikhi; Ingrid Cristian; Patricia G Wheeler; Carrie Crain; Dina Zand; Veronique Weinstein; Hilary J Vernon; Rebecca McClellan; Vidya Krishnamurthy; Patrik Vitazka; Francisca Millan; Wendy K Chung

doi:10.1101/mcs.a000455

De novo POGZ mutations are associated with neurodevelopmental disorders and microcephaly

Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000455. doi: 10.1101/mcs.a000455.

Authors

Yizhou Ye¹, Megan T Cho¹, Kyle Retterer¹, Nora Alexander¹, Tawfeg Ben-Omran², Mariam Al-Mureikhi², Ingrid Cristian³, Patricia G Wheeler³, Carrie Crain³, Dina Zand⁴, Veronique Weinstein⁴, Hilary J Vernon⁵, Rebecca McClellan⁵, Vidya Krishnamurthy⁶, Patrik Vitazka¹, Francisca Millan¹, Wendy K Chung⁷

Affiliations

¹ GeneDx, Gaithersburg, Maryland 20877, USA;
² Clinical and Metabolic Genetics, Hamad Medical Corporation, Doha, Qatar;
³ Nemours Children's Hospital, Orlando, Florida 32827, USA;
⁴ Children's National Medical Center, Washington, D.C. 20010, USA;
⁵ Kennedy Krieger Institute, Baltimore, Maryland 21205, USA;
⁶ Pediatrics and Genetics, Alpharetta, Georgia 30005, USA;
⁷ Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York 10032, USA.

Abstract

Seven patients with similar phenotypes of developmental delay and microcephaly were found by whole-exome sequencing to have de novo loss-of-function mutations in POGZ. POGZ is a pogo transposable element-derived protein with a zinc finger cluster. The protein is involved in normal kinetochore assembly and mitotic sister chromatid cohesion and mitotic chromosome segregation. POGZ deficiency may affect mitosis, disrupting brain development and function.

Keywords: intellectual disability, severe; microcephaly; severe global developmental delay.