POGZPogo transposable element with ZNF domain

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

New Scoring Scheme

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population. Functional analysis of two previously reported inherited missense variants in the POGZ gene that were identified in ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort demonstrated that these variants resulted in aberrant subcellular localization in transfected HEK293 cells, as well as a failure to rescue deficits in neurite and dendritic spine development in cultured mouse cortical neurons with Pogz knockdown (Zhao et al., 2019). The authors also observed a significant burden of rare POGZ missense variants in ASD cases compared to controls (P = 4.6E-05, odds ratio 3.96).

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene were initially identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene in Neale et al., 2012 (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene in Iossifov et al., 2012 (PMID 22542183). No likely gene-disruptive variants in POGZ were observed in controls (although many missense variants have been observed in EVS). A third de novo LoF variant in the POGZ gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014 (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified POGZ as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic intellectual disability. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo LoF variants in POGZ were identified in PMID 26739615 in individuals with developmental delay/intellectual disability and, in two cases, ASD. A review of clinical information in individuals with POGZ variants in PMID 26739615 identified shared phentoypic features (developmental delay/intellectual disability, hypotonia, behavioral abnormalities, similar facial features) and proposed that POGZ LoF variants were responsible for a form of syndromic ID. Additional LoF variants in POGZ were identified in previously unreported cases with developmental delay/intellectual disability and/or ASD in PMID 26942287. The authors of this report estimated that protein-truncating POGZ variants were significantly enriched in ASD and/or ID individuals in comparison to the general population (p=4.19E-13, odds ratio 35.8), and that the penetrance of POGZ LoF variant was 65.9% given the incidence of ID (5.12%) in the general population.

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS). A third de novo LoF variant in the POGZ gene was recently identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified POGZ as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS).

Description

De novo variants in the POGZ gene have been identified in autistic probands in two separate reports. In the first, 1 of 175 de novo frameshift variants was found in the POGZ gene (PMID 22495311). In the other, 1 of 343 likely gene-disrupting variants was found in the POGZ gene (PMID 22542183). no controls (many missense have been observed in EVS).