We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS.
Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2gps/gps) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 x 10-7).
Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2gps/gps) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 x 10-7).
The autosomal recessive form of GPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule trafficking in megakaryocytes, the platelet progenitors.
The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation.
In addition, GPS treatment markedly suppressed the expression of phosphorylated (p)-ERK, nuclear factor (NF)-κB p65 and cyclin D1, and increased the synthesis of p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and western blotting analyses.
In addition, GPS treatment markedly suppressed the expression of phosphorylated (p)-ERK, nuclear factor (NF)-κB p65 and cyclin D1, and increased the synthesis of p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and western blotting analyses.
In addition, GPS treatment markedly suppressed the expression of phosphorylated (p)-ERK, nuclear factor (NF)-κB p65 and cyclin D1, and increased the synthesis of p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and western blotting analyses.
In addition, GPS treatment markedly suppressed the expression of phosphorylated (p)-ERK, nuclear factor (NF)-κB p65 and cyclin D1, and increased the synthesis of p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and western blotting analyses.
In addition, GPS treatment markedly suppressed the expression of phosphorylated (p)-ERK, nuclear factor (NF)-κB p65 and cyclin D1, and increased the synthesis of p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and western blotting analyses.
Based on this new model, the developed simulator can present how the GPS signals (L1 and L2 carrier frequencies, C/A, P(Y) and L2C modulations) are transmitted (scattered and absorbed) through vegetation medium and received by GPS receivers.
For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10).
For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10).
For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10).
The phenotypic spectrum of KAT6B mutations has been expanding since identification of KAT6B mutations in genitopatellar syndrome (GPS) and Say Barber Biesecker Young Simpson (SBBYS) syndrome patients.
The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS.
Loss-of-function mutations in the human <i>NBEAL2</i> gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets.
This study shows for the first time proteins interacting with Nbeal2 and points to the dysregulation of the canonical signaling pathway of Dock7 as a possible cause of the aberrant formation of platelets in GPS cases and <i>Nbeal2-</i>deficient mice.
This study shows for the first time proteins interacting with Nbeal2 and points to the dysregulation of the canonical signaling pathway of Dock7 as a possible cause of the aberrant formation of platelets in GPS cases and <i>Nbeal2-</i>deficient mice.