A de novo mutation in the X-linked PAK3 gene is the underlying cause of intellectual disability and macrocephaly in monozygotic twins

Jozef Hertecant, Makanko Komara, Aslam Nagi, Olfat Al-Zaabi, Waseem Fathallah, Hong Cui, Yaping Yang, Christine M. Eng, Mohammad Al Sorkhy, Mohammad A. Ghattas, Lihadh Al-Gazali, Bassam R. Ali

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Pathogenic variants in theP21 protein (Cdc42/Rac)-activated kinase 3gene (PAK3) lead to a rare non syndromic X-linked intellectual disability. The protein encoded by this gene forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1 proteins which then mediates a variety of cellular processes. So far, mutations in PAK3 gene have been reported in few families affected with intellectual disability associated with neurological manifestations such as speech defect, behavioral problem, brain structural abnormalities, microcephaly and cerebral palsy. In this study whole exome sequencing revealed a de novo likely pathogenic variant in PAK3 gene in monozygotic twins presented with intellectual disability, speech delay, behavioral problems and macrocephaly. Macrocephaly was noticed in our patients from birth at 35 weeks of gestation. This aspect of the phenotype has not been previously reported in other documented cases with pathogenic mutations in PAK3 gene. Our findings extend the phenotype of this disorder to include macrocephaly and offers further clues to the importance of the serine/threonine-protein kinase 3 (PAK3) protein in brain development and function.

Original languageEnglish
Pages (from-to)212-216
Number of pages5
JournalEuropean Journal of Medical Genetics
Volume60
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • Intellectual disability
  • Macrocephaly
  • PAK3
  • X-linked
  • de novo mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'A de novo mutation in the X-linked PAK3 gene is the underlying cause of intellectual disability and macrocephaly in monozygotic twins'. Together they form a unique fingerprint.

Cite this