Dataset Information

Autosomal Recessive CD70 Deficiency

ABSTRACT:

We describe four patients from two unrelated families of different ethnicities who had primary immunodeficiency predominantly manifesting as susceptibility to EBV-related diseases. We performed whole exome sequencing (P1 and P2 from family 1) or whole genome sequencing (P4 and both parents from family 2) in those two families and identified homozygous frameshift or in-frame deletions in CD70 in these patients which abolished either CD70 surface expression or binding to its counter structure CD27. Sanger sequencing identified the same homozygous CD70 mutation in P3, which is not included in the dbGaP submission. Autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of CD27 deficiency.

PROVIDER: phs001245 | dbGaP |

SECONDARY ACCESSION(S): PRJNA353543PRJNA353544

REPOSITORIES: dbGaP

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Project description:Phosphatase activities on PI(3,4,5)P3 and PI(3,4)P2 This model describes the action of various phosphatases on PI(3,4,5)P3 and PI(3,4)P2, in response to a stimulation by EGF. It contains boolean switches to simulate knock-down and knock-out of phosphatases as well as inhibition of PI3 kinase. This model is described in the article: PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E. Anderson, David Barneda, P?nar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y. Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T. Hawkins and Len R. Stephens Molecular Cell Abstract: The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN. This model is hosted on BioModels Database and identified by: MODEL1704190000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Autosomal Recessive CD70 Deficiency

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