Loss of function of SVBP leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Iqbal Z, Tawamie H, Ba W, Reis A, Halak BA, Sticht H, Uebe S, Kasri NN, Riazuddin S, van Bokhoven H, Abou Jamra R
Zeitschrift: Genetics in Medicine
Jahr der Veröffentlichung: 2019
ISSN: 1098-3600


Abstract

Purpose: Identifying and characterizing novel causes of autosomal recessive intellectual disability based on systematic clinical and genetic evaluation, followed by functional experiments. Methods: Clinical examinations, genome-wide positional mapping, and sequencing were followed by quantitative polymerase chain reaction and western blot of the protein SVBP and its interaction partners. We then knocked down the gene in rat primary hippocampal neurons and evaluated the consequences on synapses. Results: We identified a founder, homozygous stop-gain variant in SVBP (c.82C>T; p.[Gln28*]) in four affected individuals from two independent families with intellectual disability, microcephaly, ataxia, and muscular hypotonia. SVBP encodes a small chaperone protein that transports and stabilizes two angiogenesis regulators, VASH1 and VASH2. The altered protein is unstable and nonfunctional since transfected HeLa cells with mutant SVBP did not reveal evidence for immunoreactive SVBP protein fragments and cotransfection with VASH1 showed a severe reduction of VASH1 in medium and cell lysate. Knocking down Svbp in rat primary hippocampal neurons led to a significant decrease in the number of excitatory synapses. Conclusion: SVBP is not only involved in angiogenesis, but also has vital functions in the central nervous system. Biallelic loss-of-function variants in SVBP lead to intellectual disability.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Sticht, Heinrich Prof. Dr.
Professur für Bioinformatik
Tawamie, Hasan
Lehrstuhl für Humangenetik
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut


Einrichtungen weiterer Autorinnen und Autoren

PIMS Pakistan Institute of Medical Sciences
Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC)


Zitierweisen

APA:
Iqbal, Z., Tawamie, H., Ba, W., Reis, A., Halak, B.A., Sticht, H.,... Abou Jamra, R. (2019). Loss of function of SVBP leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia. Genetics in Medicine. https://dx.doi.org/10.1038/s41436-018-0415-8

MLA:
Iqbal, Zafar, et al. "Loss of function of SVBP leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia." Genetics in Medicine (2019).

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Zuletzt aktualisiert 2019-12-07 um 13:08