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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

Comparative genomic hybridisation (CGH) array analysis. CGH array testing mapped the approximate position of the deletion, at coordinates 120.58–120.70 Mb, within chromosome 2. The 400K array data shown here is for Twin A. The central grey bar indicates gene PTPN4. The x axis shows the hg19 coordinates. This image is derived from the CGH Fusion software: InfoQuant Ltd (London, UK). Note that the segmentation algorithm used here may have underestimated the distal extent of the deletion (see arrow). Within the ISCN terminology, the deletion was reported as extending from 120,584,760 to 120,726,563.
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fig1: Comparative genomic hybridisation (CGH) array analysis. CGH array testing mapped the approximate position of the deletion, at coordinates 120.58–120.70 Mb, within chromosome 2. The 400K array data shown here is for Twin A. The central grey bar indicates gene PTPN4. The x axis shows the hg19 coordinates. This image is derived from the CGH Fusion software: InfoQuant Ltd (London, UK). Note that the segmentation algorithm used here may have underestimated the distal extent of the deletion (see arrow). Within the ISCN terminology, the deletion was reported as extending from 120,584,760 to 120,726,563.

Mentions: CGH array analysis of the twins identified a deletion (arr[hg19] 2q14.2(120,584,760-120,726,563) × 1 dn), with a minimum size of 90 Kb (Chr2.hg19:g. 120,584,760_120,726,563del) and a maximum size of 160 Kb (Chr2.hg19:g. 120,579,294 _120,734,950del), Figure 1. This deletion was not seen in their healthy parents or their two healthy siblings. This region contains a single gene, protein tyrosine phosphatase, non-receptor type 4 (PTPN4/PTPMEG), GenBank ref NC_000002. This phosphatase is expressed predominately in the brain and testis21 and knockout of the Drosophila and murine orthologues results in neurological abnormalities.22, 23 This essential role of PTPN4 in neuronal development and function suggests that PTPN4 is a good candidate gene for the variant RTT phenotype seen in the twins.


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)

Comparative genomic hybridisation (CGH) array analysis. CGH array testing mapped the approximate position of the deletion, at coordinates 120.58–120.70 Mb, within chromosome 2. The 400K array data shown here is for Twin A. The central grey bar indicates gene PTPN4. The x axis shows the hg19 coordinates. This image is derived from the CGH Fusion software: InfoQuant Ltd (London, UK). Note that the segmentation algorithm used here may have underestimated the distal extent of the deletion (see arrow). Within the ISCN terminology, the deletion was reported as extending from 120,584,760 to 120,726,563.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Comparative genomic hybridisation (CGH) array analysis. CGH array testing mapped the approximate position of the deletion, at coordinates 120.58–120.70 Mb, within chromosome 2. The 400K array data shown here is for Twin A. The central grey bar indicates gene PTPN4. The x axis shows the hg19 coordinates. This image is derived from the CGH Fusion software: InfoQuant Ltd (London, UK). Note that the segmentation algorithm used here may have underestimated the distal extent of the deletion (see arrow). Within the ISCN terminology, the deletion was reported as extending from 120,584,760 to 120,726,563.
Mentions: CGH array analysis of the twins identified a deletion (arr[hg19] 2q14.2(120,584,760-120,726,563) × 1 dn), with a minimum size of 90 Kb (Chr2.hg19:g. 120,584,760_120,726,563del) and a maximum size of 160 Kb (Chr2.hg19:g. 120,579,294 _120,734,950del), Figure 1. This deletion was not seen in their healthy parents or their two healthy siblings. This region contains a single gene, protein tyrosine phosphatase, non-receptor type 4 (PTPN4/PTPMEG), GenBank ref NC_000002. This phosphatase is expressed predominately in the brain and testis21 and knockout of the Drosophila and murine orthologues results in neurological abnormalities.22, 23 This essential role of PTPN4 in neuronal development and function suggests that PTPN4 is a good candidate gene for the variant RTT phenotype seen in the twins.

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