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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

Ptpn4 expression reduced in the brain of the Mecp2tm1Tam mouse model of RTT. Quantitation of Ptpn4 expression in the cerebellum and hippocampus of presymptomatic and symptomatic Mecp2y/+ (wild type) and Mecp2y/− () mice (n=5, error bars=SD).
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fig2: Ptpn4 expression reduced in the brain of the Mecp2tm1Tam mouse model of RTT. Quantitation of Ptpn4 expression in the cerebellum and hippocampus of presymptomatic and symptomatic Mecp2y/+ (wild type) and Mecp2y/− () mice (n=5, error bars=SD).

Mentions: Several Mecp2 knockout and knock-in mice have been developed to model the RTT phenotype. Although the phenotype of the Ptpn4 mouse is mild compared with that of the Mecp2 mouse, both models display impairment of motor co-ordination and learning. We therefore examined whether Ptpn4 expression is dysregulated in the brain of the Mecp2tm1Tam mouse. qPCR analysis of the Ptpn4 transcript (Figure 2) demonstrated a significant reduction of Ptpn4 levels in both cerebellum and hippocampus of symptomatic Mecp2−/y mice, while in the presymptomatic animals a significant reduction was only observed in the cerebellum but not in the hippocampus. A brain region-specific dysregulation of Ptpn4 in presymptomatic Mecp2−/y mice thus became more widespread with progression of the disease phenotype.


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)

Ptpn4 expression reduced in the brain of the Mecp2tm1Tam mouse model of RTT. Quantitation of Ptpn4 expression in the cerebellum and hippocampus of presymptomatic and symptomatic Mecp2y/+ (wild type) and Mecp2y/− () mice (n=5, error bars=SD).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Ptpn4 expression reduced in the brain of the Mecp2tm1Tam mouse model of RTT. Quantitation of Ptpn4 expression in the cerebellum and hippocampus of presymptomatic and symptomatic Mecp2y/+ (wild type) and Mecp2y/− () mice (n=5, error bars=SD).
Mentions: Several Mecp2 knockout and knock-in mice have been developed to model the RTT phenotype. Although the phenotype of the Ptpn4 mouse is mild compared with that of the Mecp2 mouse, both models display impairment of motor co-ordination and learning. We therefore examined whether Ptpn4 expression is dysregulated in the brain of the Mecp2tm1Tam mouse. qPCR analysis of the Ptpn4 transcript (Figure 2) demonstrated a significant reduction of Ptpn4 levels in both cerebellum and hippocampus of symptomatic Mecp2−/y mice, while in the presymptomatic animals a significant reduction was only observed in the cerebellum but not in the hippocampus. A brain region-specific dysregulation of Ptpn4 in presymptomatic Mecp2−/y mice thus became more widespread with progression of the disease phenotype.

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