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Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.

Williamson SL, Ellaway CJ, Peters GB, Pelka GJ, Tam PP, Christodoulou J - Eur. J. Hum. Genet. (2014)

Bottom Line: Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT.Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype.Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.

View Article: PubMed Central - PubMed

Affiliation: NSW Centre for Rett Syndrome Research, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

ABSTRACT
Rett syndrome (RTT), a neurodevelopmental disorder that predominantly affects females, is primarily caused by variants in MECP2. Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT. Individuals with phenotypes suggestive of RTT are typically screened for variants in MECP2 and then subsequently the other genes dependent on the specific phenotype. Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype. Here we report a de novo deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in identical twins with a RTT-like phenotype. We also demonstrate the reduced expression of Ptpn4 in a Mecp2 mouse model of RTT, as well as the activation of the PTPN4 promoter by MeCP2. Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.

No MeSH data available.


Related in: MedlinePlus

MeCP2 enhances PTPN4 promoter-driven gene expression in SHSY-5Y cells. Relative luminescence of the promoterless luciferase vector (pcBG99-basic) and the PTPN4 promoter-driven luciferase vector (pcBG99-PTPN4), with and without MeCP2. Two independent experiments with triplicate transfections and duplicate readings were performed. Error bars=SD.
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fig4: MeCP2 enhances PTPN4 promoter-driven gene expression in SHSY-5Y cells. Relative luminescence of the promoterless luciferase vector (pcBG99-basic) and the PTPN4 promoter-driven luciferase vector (pcBG99-PTPN4), with and without MeCP2. Two independent experiments with triplicate transfections and duplicate readings were performed. Error bars=SD.

Mentions: Given the inconclusive results of the ChIP assays, we next investigated the ability of MeCP2 to mediate the expression PTPN4 promoter using a luciferase reporter vector containing the PTPN4 promoter (pcBG99-PTPN4). In SH-SY5Y cells, the level of luciferase expression in the presence of MeCP2 was 2.1±0.67-fold of that of pcBG99-PTPN4 alone (Figure 4), indicating that MeCP2 is capable of acting as a transcriptional activator to the PTPN4 promoter.


Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.

Williamson SL, Ellaway CJ, Peters GB, Pelka GJ, Tam PP, Christodoulou J - Eur. J. Hum. Genet. (2014)

MeCP2 enhances PTPN4 promoter-driven gene expression in SHSY-5Y cells. Relative luminescence of the promoterless luciferase vector (pcBG99-basic) and the PTPN4 promoter-driven luciferase vector (pcBG99-PTPN4), with and without MeCP2. Two independent experiments with triplicate transfections and duplicate readings were performed. Error bars=SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4538211&req=5

fig4: MeCP2 enhances PTPN4 promoter-driven gene expression in SHSY-5Y cells. Relative luminescence of the promoterless luciferase vector (pcBG99-basic) and the PTPN4 promoter-driven luciferase vector (pcBG99-PTPN4), with and without MeCP2. Two independent experiments with triplicate transfections and duplicate readings were performed. Error bars=SD.
Mentions: Given the inconclusive results of the ChIP assays, we next investigated the ability of MeCP2 to mediate the expression PTPN4 promoter using a luciferase reporter vector containing the PTPN4 promoter (pcBG99-PTPN4). In SH-SY5Y cells, the level of luciferase expression in the presence of MeCP2 was 2.1±0.67-fold of that of pcBG99-PTPN4 alone (Figure 4), indicating that MeCP2 is capable of acting as a transcriptional activator to the PTPN4 promoter.

Bottom Line: Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT.Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype.Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.

View Article: PubMed Central - PubMed

Affiliation: NSW Centre for Rett Syndrome Research, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

ABSTRACT
Rett syndrome (RTT), a neurodevelopmental disorder that predominantly affects females, is primarily caused by variants in MECP2. Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT. Individuals with phenotypes suggestive of RTT are typically screened for variants in MECP2 and then subsequently the other genes dependent on the specific phenotype. Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype. Here we report a de novo deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in identical twins with a RTT-like phenotype. We also demonstrate the reduced expression of Ptpn4 in a Mecp2 mouse model of RTT, as well as the activation of the PTPN4 promoter by MeCP2. Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.

No MeSH data available.


Related in: MedlinePlus