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Variants in DOCK3 cause developmental delay and hypotonia.

ABSTRACT: The DOCK3 gene encodes the Dedicator of cytokinesis 3 (DOCK3) protein, which belongs to the family of guanine nucleotide exchange factors and is expressed almost exclusively in the brain and spinal cord. We used whole exome sequencing (WES) to investigate the molecular cause of developmental delay and hypotonia in three unrelated probands. WES identified truncating and splice site variants in Patient 1 and compound heterozygous and homozygous missense variants in Patients 2 and 3, respectively. We studied the effect of the three missense variants in vitro by using site-directed mutagenesis and pull-down assay and show that the induction of Rac1 activation was significantly lower in DOCK3 mutant cells compared with wild type human DOCK3 (P?

SUBMITTER: Wiltrout K

PROVIDER: S-EPMC6777627 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Variants in DOCK3 cause developmental delay and hypotonia.

Wiltrout Kimberly K Ferrer Alejandro A van de Laar Ingrid I Namekata Kazuhiko K Harada Takayuki T Klee Eric W EW Zimmerman Michael T MT Cousin Margot A MA Kempainen Jennifer L JL Babovic-Vuksanovic Dusica D van Slegtenhorst Marjon A MA Aarts-Tesselaar Coranne D CD Schnur Rhonda E RE Andrews Marisa M Shinawi Marwan M

European journal of human genetics : EJHG 20190411 8

The DOCK3 gene encodes the Dedicator of cytokinesis 3 (DOCK3) protein, which belongs to the family of guanine nucleotide exchange factors and is expressed almost exclusively in the brain and spinal cord. We used whole exome sequencing (WES) to investigate the molecular cause of developmental delay and hypotonia in three unrelated probands. WES identified truncating and splice site variants in Patient 1 and compound heterozygous and homozygous missense variants in Patients 2 and 3, respectively. ...[more]

PMID: 30976111

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