• Medientyp: E-Artikel
  • Titel: DOCK3‐related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia
  • Beteiligte: Iwata‐Otsubo, Aiko; Ritter, Alyssa L.; Weckselbatt, Brooke; Ryan, Nicole R.; Burgess, David; Conlin, Laura K.; Izumi, Kosuke
  • Erschienen: Wiley, 2018
  • Erschienen in: American Journal of Medical Genetics Part A
  • Umfang: 241-245
  • Sprache: Englisch
  • DOI: 10.1002/ajmg.a.38517
  • ISSN: 1552-4825; 1552-4833
  • Schlagwörter: Genetics (clinical) ; Genetics
  • Zusammenfassung: <jats:sec><jats:label /><jats:p>Dedicator of cytokinesis (DOCK) family are evolutionary conserved guanine nucleotide exchange factors (GEFs) for the Rho GTPases, Rac, and Cdc42. DOCK3 functions as a GEF for Rac1, and plays an important role in promoting neurite and axonal growth by stimulating actin dynamics and microtubule assembly pathways in the central nervous system. Here we report a boy with developmental delay, hypotonia, and ataxia due to biallelic <jats:italic>DOCK3</jats:italic> deletion. Chromosomal single nucleotide polymorphism (SNP) microarray analysis detected a 170 kb homozygous deletion including exons 6–12 of the <jats:italic>DOCK3</jats:italic> gene at 3p21.2. Symptoms of our proband resembles a phenotype of <jats:italic>Dock3</jats:italic> knockout mice exhibiting sensorimotor impairments. Furthermore, our proband has clinical similarities with two siblings with compound heterozygous loss‐of‐function mutations of <jats:italic>DOCK3</jats:italic> reported in [Helbig, Mroske, Moorthy, Sajan, and Velinov (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#ajmga38517-bib-0006" />); <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://doi.org/10.1111/cge.12995">https://doi.org/10.1111/cge.12995</jats:ext-link>]. Biallelic <jats:italic>DOCK3</jats:italic> mutations cause a neurodevelopmental disorder characterized by unsteady gait, hypotonia, and developmental delay.</jats:p></jats:sec>
  • Beschreibung: <jats:sec><jats:label /><jats:p>Dedicator of cytokinesis (DOCK) family are evolutionary conserved guanine nucleotide exchange factors (GEFs) for the Rho GTPases, Rac, and Cdc42. DOCK3 functions as a GEF for Rac1, and plays an important role in promoting neurite and axonal growth by stimulating actin dynamics and microtubule assembly pathways in the central nervous system. Here we report a boy with developmental delay, hypotonia, and ataxia due to biallelic <jats:italic>DOCK3</jats:italic> deletion. Chromosomal single nucleotide polymorphism (SNP) microarray analysis detected a 170 kb homozygous deletion including exons 6–12 of the <jats:italic>DOCK3</jats:italic> gene at 3p21.2. Symptoms of our proband resembles a phenotype of <jats:italic>Dock3</jats:italic> knockout mice exhibiting sensorimotor impairments. Furthermore, our proband has clinical similarities with two siblings with compound heterozygous loss‐of‐function mutations of <jats:italic>DOCK3</jats:italic> reported in [Helbig, Mroske, Moorthy, Sajan, and Velinov (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#ajmga38517-bib-0006" />); <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://doi.org/10.1111/cge.12995">https://doi.org/10.1111/cge.12995</jats:ext-link>]. Biallelic <jats:italic>DOCK3</jats:italic> mutations cause a neurodevelopmental disorder characterized by unsteady gait, hypotonia, and developmental delay.</jats:p></jats:sec>
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