title: Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.
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 null 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.
authors.affiliation: NSW Centre for Rett Syndrome Research, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Williamson
authors.affiliation: 1] NSW Centre for Rett Syndrome Research, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Ellaway
authors.affiliation: 1] Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia [2] Sydney Genome Diagnostics, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Greg B
authors.initials: GB
authors.lastname: Peters
authors.affiliation: Embryology Unit, Children's Medical Research Institute, Sydney, New South Wales, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pelka
authors.affiliation: 1] Embryology Unit, Children's Medical Research Institute, Sydney, New South Wales, Australia [2] Discipline of Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Tam
authors.affiliation: 1] NSW Centre for Rett Syndrome Research, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D000293:Adolescent; D000818:Animals; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology; D002889:Chromosomes, Human, Pair 2 / Q000737:chemistry; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005838:Genotype; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4 / Q000172:deficiency / Q000235:genetics*; D015518:Rett Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014430:Twins, Monozygotic
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; C516658:PTPN4 protein, human; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4