The Experts below are selected from a list of 378 Experts worldwide ranked by ideXlab platform

Yi-qing Yang - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome
    2016
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an over-whelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carri-er’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functiona

  • pitx2 loss of function mutation contributes to congenital Endocardial Cushion Defect and axenfeld rieger syndrome
    PLOS ONE, 2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

  • PITX2 mutation associated with Endocardial Cushion Defect and Axenfeld-Rieger syndrome.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    (A) Sequence electropherograms showing the heterozygous PITX2 mutation compared with its control. The arrow indicates the heterozygous nucleotides of C/T in the proband (mutant) or the homozygous nucleotides of C/C in the corresponding control individual (wild-type). The rectangle signifies the nucleotides comprising a codon of PITX2. (B) Schematic diagrams showing the structural domains of wild-type and mutant PITX2 proteins with the disease related mutation indicated. The mutation found in patients with Endocardial Cushion Defect and Axenfeld-Rieger syndrome is shown above the structural domains of the mutant PITX2 proteins. NH2 denotes amino-terminus; TAD1, transcriptional activation domain 1; HD, homeodomain; NLS, nuclear localization signal; TID1, transcriptional inhibitory domain 1; TAD2, transcriptional activation domain 2; TID2, transcriptional inhibitory domain 2; COOH, carboxyl-terminus. (C) Pedigree structure of the family with Endocardial Cushion Defect and Axenfeld-Rieger syndrome. Family members are identified by generations and numbers. Square indicates male family member; circle, female member; symbol with a slash, the deceased member; closed symbol, affected member; open symbol, unaffected member; arrow, proband; “+”, carrier of the heterozygous mutation; “–”, non-carrier.

  • Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    M, male; F, female; ECD, Endocardial Cushion Defect; MVC, mitral valve cleft; RAA, right aortic arch; TGA, transposition of the great arteries; OD, oligodontia; MH, maxillary hypoplasia; IH, iris hypoplasia; UH, umbilical hernia; NA, not available; +/–, heterozygote.aAge at death.Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.

  • Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    CHD, congenital heart disease; VSD, ventricular septal Defect; ASD, atrial septal Defect; PDA, patent ductus arteriosus; ECD, Endocardial Cushion Defect; AS, aortic stenosis; PA, pulmonary atresia; CoA, coarctation of the aorta; PS, pulmonary stenosis; TA, truncusarteriosus; HLHS, hypoplastic left heart syndrome; TOF, tetralogy of Fallot; DORV, double outlet of right ventricle; TGA, transposition of great arteries.Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.

Cui-mei Zhao - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome
    2016
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an over-whelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carri-er’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functiona

  • pitx2 loss of function mutation contributes to congenital Endocardial Cushion Defect and axenfeld rieger syndrome
    PLOS ONE, 2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

  • PITX2 mutation associated with Endocardial Cushion Defect and Axenfeld-Rieger syndrome.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    (A) Sequence electropherograms showing the heterozygous PITX2 mutation compared with its control. The arrow indicates the heterozygous nucleotides of C/T in the proband (mutant) or the homozygous nucleotides of C/C in the corresponding control individual (wild-type). The rectangle signifies the nucleotides comprising a codon of PITX2. (B) Schematic diagrams showing the structural domains of wild-type and mutant PITX2 proteins with the disease related mutation indicated. The mutation found in patients with Endocardial Cushion Defect and Axenfeld-Rieger syndrome is shown above the structural domains of the mutant PITX2 proteins. NH2 denotes amino-terminus; TAD1, transcriptional activation domain 1; HD, homeodomain; NLS, nuclear localization signal; TID1, transcriptional inhibitory domain 1; TAD2, transcriptional activation domain 2; TID2, transcriptional inhibitory domain 2; COOH, carboxyl-terminus. (C) Pedigree structure of the family with Endocardial Cushion Defect and Axenfeld-Rieger syndrome. Family members are identified by generations and numbers. Square indicates male family member; circle, female member; symbol with a slash, the deceased member; closed symbol, affected member; open symbol, unaffected member; arrow, proband; “+”, carrier of the heterozygous mutation; “–”, non-carrier.

  • Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    M, male; F, female; ECD, Endocardial Cushion Defect; MVC, mitral valve cleft; RAA, right aortic arch; TGA, transposition of the great arteries; OD, oligodontia; MH, maxillary hypoplasia; IH, iris hypoplasia; UH, umbilical hernia; NA, not available; +/–, heterozygote.aAge at death.Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.

  • Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    CHD, congenital heart disease; VSD, ventricular septal Defect; ASD, atrial septal Defect; PDA, patent ductus arteriosus; ECD, Endocardial Cushion Defect; AS, aortic stenosis; PA, pulmonary atresia; CoA, coarctation of the aorta; PS, pulmonary stenosis; TA, truncusarteriosus; HLHS, hypoplastic left heart syndrome; TOF, tetralogy of Fallot; DORV, double outlet of right ventricle; TGA, transposition of great arteries.Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.

Fang Yuan - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome
    2016
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an over-whelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carri-er’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functiona

  • pitx2 loss of function mutation contributes to congenital Endocardial Cushion Defect and axenfeld rieger syndrome
    PLOS ONE, 2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

  • PITX2 mutation associated with Endocardial Cushion Defect and Axenfeld-Rieger syndrome.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    (A) Sequence electropherograms showing the heterozygous PITX2 mutation compared with its control. The arrow indicates the heterozygous nucleotides of C/T in the proband (mutant) or the homozygous nucleotides of C/C in the corresponding control individual (wild-type). The rectangle signifies the nucleotides comprising a codon of PITX2. (B) Schematic diagrams showing the structural domains of wild-type and mutant PITX2 proteins with the disease related mutation indicated. The mutation found in patients with Endocardial Cushion Defect and Axenfeld-Rieger syndrome is shown above the structural domains of the mutant PITX2 proteins. NH2 denotes amino-terminus; TAD1, transcriptional activation domain 1; HD, homeodomain; NLS, nuclear localization signal; TID1, transcriptional inhibitory domain 1; TAD2, transcriptional activation domain 2; TID2, transcriptional inhibitory domain 2; COOH, carboxyl-terminus. (C) Pedigree structure of the family with Endocardial Cushion Defect and Axenfeld-Rieger syndrome. Family members are identified by generations and numbers. Square indicates male family member; circle, female member; symbol with a slash, the deceased member; closed symbol, affected member; open symbol, unaffected member; arrow, proband; “+”, carrier of the heterozygous mutation; “–”, non-carrier.

  • Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    M, male; F, female; ECD, Endocardial Cushion Defect; MVC, mitral valve cleft; RAA, right aortic arch; TGA, transposition of the great arteries; OD, oligodontia; MH, maxillary hypoplasia; IH, iris hypoplasia; UH, umbilical hernia; NA, not available; +/–, heterozygote.aAge at death.Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.

  • Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    CHD, congenital heart disease; VSD, ventricular septal Defect; ASD, atrial septal Defect; PDA, patent ductus arteriosus; ECD, Endocardial Cushion Defect; AS, aortic stenosis; PA, pulmonary atresia; CoA, coarctation of the aorta; PS, pulmonary stenosis; TA, truncusarteriosus; HLHS, hypoplastic left heart syndrome; TOF, tetralogy of Fallot; DORV, double outlet of right ventricle; TGA, transposition of great arteries.Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.

Xing-biao Qiu - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome
    2016
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an over-whelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carri-er’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functiona

  • pitx2 loss of function mutation contributes to congenital Endocardial Cushion Defect and axenfeld rieger syndrome
    PLOS ONE, 2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

  • PITX2 mutation associated with Endocardial Cushion Defect and Axenfeld-Rieger syndrome.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    (A) Sequence electropherograms showing the heterozygous PITX2 mutation compared with its control. The arrow indicates the heterozygous nucleotides of C/T in the proband (mutant) or the homozygous nucleotides of C/C in the corresponding control individual (wild-type). The rectangle signifies the nucleotides comprising a codon of PITX2. (B) Schematic diagrams showing the structural domains of wild-type and mutant PITX2 proteins with the disease related mutation indicated. The mutation found in patients with Endocardial Cushion Defect and Axenfeld-Rieger syndrome is shown above the structural domains of the mutant PITX2 proteins. NH2 denotes amino-terminus; TAD1, transcriptional activation domain 1; HD, homeodomain; NLS, nuclear localization signal; TID1, transcriptional inhibitory domain 1; TAD2, transcriptional activation domain 2; TID2, transcriptional inhibitory domain 2; COOH, carboxyl-terminus. (C) Pedigree structure of the family with Endocardial Cushion Defect and Axenfeld-Rieger syndrome. Family members are identified by generations and numbers. Square indicates male family member; circle, female member; symbol with a slash, the deceased member; closed symbol, affected member; open symbol, unaffected member; arrow, proband; “+”, carrier of the heterozygous mutation; “–”, non-carrier.

  • Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    M, male; F, female; ECD, Endocardial Cushion Defect; MVC, mitral valve cleft; RAA, right aortic arch; TGA, transposition of the great arteries; OD, oligodontia; MH, maxillary hypoplasia; IH, iris hypoplasia; UH, umbilical hernia; NA, not available; +/–, heterozygote.aAge at death.Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.

  • Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    CHD, congenital heart disease; VSD, ventricular septal Defect; ASD, atrial septal Defect; PDA, patent ductus arteriosus; ECD, Endocardial Cushion Defect; AS, aortic stenosis; PA, pulmonary atresia; CoA, coarctation of the aorta; PS, pulmonary stenosis; TA, truncusarteriosus; HLHS, hypoplastic left heart syndrome; TOF, tetralogy of Fallot; DORV, double outlet of right ventricle; TGA, transposition of great arteries.Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.

Lu-ying Peng - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome
    2016
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an over-whelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carri-er’s family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functiona

  • pitx2 loss of function mutation contributes to congenital Endocardial Cushion Defect and axenfeld rieger syndrome
    PLOS ONE, 2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    Congenital heart disease (CHD), the most common type of birth Defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic Defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with Endocardial Cushion Defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.

  • PITX2 mutation associated with Endocardial Cushion Defect and Axenfeld-Rieger syndrome.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    (A) Sequence electropherograms showing the heterozygous PITX2 mutation compared with its control. The arrow indicates the heterozygous nucleotides of C/T in the proband (mutant) or the homozygous nucleotides of C/C in the corresponding control individual (wild-type). The rectangle signifies the nucleotides comprising a codon of PITX2. (B) Schematic diagrams showing the structural domains of wild-type and mutant PITX2 proteins with the disease related mutation indicated. The mutation found in patients with Endocardial Cushion Defect and Axenfeld-Rieger syndrome is shown above the structural domains of the mutant PITX2 proteins. NH2 denotes amino-terminus; TAD1, transcriptional activation domain 1; HD, homeodomain; NLS, nuclear localization signal; TID1, transcriptional inhibitory domain 1; TAD2, transcriptional activation domain 2; TID2, transcriptional inhibitory domain 2; COOH, carboxyl-terminus. (C) Pedigree structure of the family with Endocardial Cushion Defect and Axenfeld-Rieger syndrome. Family members are identified by generations and numbers. Square indicates male family member; circle, female member; symbol with a slash, the deceased member; closed symbol, affected member; open symbol, unaffected member; arrow, proband; “+”, carrier of the heterozygous mutation; “–”, non-carrier.

  • Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    M, male; F, female; ECD, Endocardial Cushion Defect; MVC, mitral valve cleft; RAA, right aortic arch; TGA, transposition of the great arteries; OD, oligodontia; MH, maxillary hypoplasia; IH, iris hypoplasia; UH, umbilical hernia; NA, not available; +/–, heterozygote.aAge at death.Phenotypic characteristics and status of PITX2 mutation of the affected pedigree members.

  • Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.
    2015
    Co-Authors: Cui-mei Zhao, Lu-ying Peng, Xing-yuan Liu, Juan Wang, Xian-ling Zhang, Fang Yuan, Xing-biao Qiu, Yi-qing Yang
    Abstract:

    CHD, congenital heart disease; VSD, ventricular septal Defect; ASD, atrial septal Defect; PDA, patent ductus arteriosus; ECD, Endocardial Cushion Defect; AS, aortic stenosis; PA, pulmonary atresia; CoA, coarctation of the aorta; PS, pulmonary stenosis; TA, truncusarteriosus; HLHS, hypoplastic left heart syndrome; TOF, tetralogy of Fallot; DORV, double outlet of right ventricle; TGA, transposition of great arteries.Baseline clinical characteristics of the 196 unrelated patients with congenital heart disease.