scholarly journals SHORT syndrome

2020 ◽  
Author(s):  
Keyword(s):  
Short Syndrome

scholarly journals Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Clea Bárcena ◽  
Víctor Quesada ◽  
Annachiara De Sandre-Giovannoli ◽  
Diana A Puente ◽  
Joaquín Fernández-Toral ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Novel Mutation ◽  
Short Syndrome

scholarly journals Insights into the pathological mechanisms of p85α mutations using a yeast-based phosphatidylinositol 3-kinase model

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
María D. Oliver ◽  
Teresa Fernández-Acero ◽  
Sandra Luna ◽  
Isabel Rodríguez-Escudero ◽  
María Molina ◽  
...  
Keyword(s):  
Germ Line ◽  
Functional Characterization ◽  
Binding Domain ◽  
C2 Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Functional Studies ◽  
Short Syndrome ◽  
Positively Charged ◽  
Inhibitory Regulation ◽  
Phosphatidylinositol 3

In higher eukaryotes, cell proliferation is regulated by class I phosphatidylinositol 3-kinase (PI3K), which transduces stimuli received from neighboring receptors by local generation of PtdIns(3,4,5)P3 in cellular membranes. PI3K is a heterodimeric protein consisting of a regulatory and a catalytic subunit (p85 and p110 respectively). Heterologous expression of p110α in Saccharomyces cerevisiae leads to toxicity by conversion of essential PtdIns(4,5)P2 into futile PtdIns(3,4,5)P3, providing a humanized yeast model for functional studies on this pathway. Here, we report expression and functional characterization in yeast of all regulatory and catalytic human PI3K isoforms, and exploitation of the most suitable setting to functionally assay panels of tumor- and germ line-associated PI3K mutations, with indications to the limits of the system. The activity of p110α in yeast was not compromised by truncation of its N-terminal adaptor-binding domain (ABD) or inactivation of the Ras-binding domain (RBD). In contrast, a cluster of positively charged residues at the C2 domain was essential. Expression of a membrane-driven p65α oncogenic-truncated version of p85α, but not the full-length protein, led to enhanced activity of α, β, and δ p110 isoforms. Mutations impairing the inhibitory regulation exerted by the p85α iSH2 domain on the C2 domain of p110α yielded the latter non-responsive to negative regulation, thus reproducing this oncogenic mechanism in yeast. However, p85α germ line mutations associated with short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome did not increase PI3K activity in this model, supporting the idea that SHORT syndrome-associated p85α mutations operate through mechanisms different from the canonical disruption of inhibitory p85–p110 interactions typical of cancer.

scholarly journals A novel PIK3R1 mutation of SHORT syndrome in a Chinese female with diffuse thyroid disease: a case report and review of literature

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Liying Sun ◽  
Qianwen Zhang ◽  
Qun Li ◽  
Yijun Tang ◽  
Yirou Wang ◽  
...  
Keyword(s):  
Case Report ◽  
Short Stature ◽  
Thyroid Disease ◽  
Nonsense Mutation ◽  
Intrauterine Growth Restriction ◽  
De Novo ◽  
Protein Translation ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Short Syndrome

Abstract Background SHORT syndrome is a rare genetic disease named with the acronyms of short stature, hyper-extensibility of joints, ocular depression, Rieger anomaly and teething delay. It is inherited in an autosomal dominant manner confirmed by the identification of heterozygous mutations in PIK3R1. This study hereby presents a 15-year-old female with intrauterine growth restriction, short stature, teething delay, characteristic facial gestalts who was identified a novel de novo nonsense mutation in PIK3R1. Case presentation The proband was admitted to our department due to irregular menstrual cycle and hirsutism with short stature, who had a history of intrauterine growth restriction and presented with short stature, teething delay, characteristic facial gestalts, hirsutism, and thyroid disease. Whole-exome sequencing and Sanger sequencing revealed c.1960C > T, a novel de novo nonsense mutation, leading to the termination of protein translation (p. Gln654*). Conclusions This is the first case report of SHORT syndrome complicated with thyroid disease in China, identifying a novel de novo heterozygous nonsense mutation in PIK3R1 gene (p. Gln654*). The phenotypes are mildly different from other cases previously described in the literature, in which our patient presents with lipoatrophy, facial feature, and first reported thyroid disease. Thyroid disease may be a new clinical symptom of patients with SHORT syndrome.

scholarly journals SHORT syndrome due to a novel de novo mutation in PRKCE (Protein Kinase Cɛ) impairing TORC2-dependent AKT activation

2017 ◽  
Vol 26 (19) ◽  
pp. 3713-3721 ◽  
Author(s):  
Diana Alcantara ◽  
Frances Elmslie ◽  
Martine Tetreault ◽  
Eric Bareke ◽  
Taila Hartley ◽  
...  
Keyword(s):  
Protein Kinase ◽  
De Novo ◽  
De Novo Mutation ◽  
Akt Activation ◽  
Short Syndrome

Report of a case and further delineation of the SHORT syndrome

1985 ◽  
Vol 22 (2) ◽  
pp. 311-314 ◽  
Author(s):  
Helga V. Toriello ◽  
Susan Wakefield ◽  
Karl Komar ◽  
James V. Higgins ◽  
Donald F. Waterman ◽  
...  
Keyword(s):  
Short Syndrome

Autosomal dominant PIK3R1 mutations cause SHORT syndrome

2013 ◽  
Vol 85 (3) ◽  
pp. 228-229 ◽  
Author(s):  
B.K. Chung ◽  
W.T. Gibson
Keyword(s):  
Autosomal Dominant ◽  
Short Syndrome

SHORT syndrome: distinctive radiographic features

1998 ◽  
Vol 7 (2) ◽  
pp. 103-107 ◽  
Author(s):  
Eric Haan ◽  
Lloyd Morris
Keyword(s):  
Radiographic Features ◽  
Short Syndrome

SHORT syndrome: a case with high hyperopia and astigmatism

2000 ◽  
Vol 21 (4) ◽  
pp. 235-238 ◽  
Author(s):  
S. Bonnel ◽  
P. Dureau ◽  
M. LeMerrer ◽  
J.L. Dufier
Keyword(s):  
Short Syndrome ◽  
High Hyperopia

scholarly journals C-terminal truncation of Pik3r1 in mice models human lipodystrophic insulin resistance uncoupled from dyslipidemia

2017 ◽  
Author(s):  
Albert Kwok ◽  
Ilona Zvetkova ◽  
Sam Virtue ◽  
Isabel Huang-Doran ◽  
Patsy Tomlinson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tyrosine Kinases ◽  
Target Genes ◽  
Ex Vivo ◽  
Liver Weight ◽  
Postnatal Growth ◽  
Regulatory Subunit ◽  
Severe Insulin Resistance ◽  
Triglyceride Content ◽  
Short Syndrome

SummaryHeterodimeric class IA phosphatidylinositol-3-kinases (PI3K) transduce signals from many receptor tyrosine kinases including the insulin receptor. PI3K recruitment to phosphotyrosines is mediated by Pik3r1 gene products including the most intensely studied PI3K regulatory subunit, p85α, which also binds and regulates the PIP3 phosphatase Pten, and the lipogenic transcription factor Xbp1. Mutations in human PIK3R1 cause SHORT syndrome, featuring lipodystrophy and severe insulin resistance which, uniquely, are uncoupled from fatty liver and dyslipidemia. We describe a novel mouse model of SHORT syndrome made by knock in of the Pik3r1 Y657X mutation. Homozygous embryos die at E11.5, while heterozygous mice exhibit pre-and postnatal growth impairment with diminished placental vascularity. Adipose tissue accretion on high fat feeding was reduced, however adipocyte size was unchanged and preadipocyte differentiation ex vivo unimpaired. Despite severe insulin resistance, heterozygous mice were hypolipidemic, and plasma adiponectin, liver weight, cholesterol, glycogen and triglyceride content were unchanged. Mild downregulation of lipogenic Srebp1, Srebp2 and Chrebp transcriptional activity but no suppression of Xbp1 target genes was seen after fasting. These findings give new insights into the developmental role of Pik3r1, and establish a model of lipodystrophic insulin resistance dissociated from dyslipidemia as seen in SHORT syndrome.

SHORT syndrome: a case with high hyperopia and astigmatism

2000 ◽  
Vol 21 (4) ◽  
pp. 235-238
Author(s):  
S. Bonnel ◽  
P. Dureau ◽  
M. LeMerrer ◽  
J.L. Dufier
Keyword(s):  
Short Syndrome ◽  
High Hyperopia
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