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Ian D Krantz - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
2016Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Alisha B. Wilkens, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such a
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12p microRNA expression in fibroblast cell lines from probands with Pallister-Killian Syndrome
Chromosome Research, 2014Co-Authors: Kosuke Izumi, Zhe Zhang, Maninder Kaur, Ian D KrantzAbstract:Pallister-Killian Syndrome is a multisystem sporadic genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, seizures, diaphragmatic hernia, and other systemic abnormalities. Pallister-Killian Syndrome is typically caused by the presence of a supernumerary isochromosome that is always present in a tissue limited mosaic pattern, resulting in tetrasomy 12p due to the two extra copies of 12p. We evaluated the potential contribution of microRNAs located on 12p to the pathogenesis of Pallister-Killian Syndrome phenotype. Using skin fibroblast cell lines from 13 probands with Pallister-Killian Syndrome and 5 normal matched controls, the expression level of 5 microRNAs located on 12p and their target gene mRNA levels were measured. All measured micro RNAs located on 12p were overexpressed in Pallister-Killian Syndrome fibroblasts, although the fold difference of the expression level was lower than copy number differences. Among the five microRNAs, miR-1244 had the highest fold difference. Many of computer-predicted target genes of miR-1244 were downregulated in Pallister-Killian Syndrome skin fibroblasts. In particular, expression levels of MEIS2 and UQCRB were significantly decreased in Pallister-Killian Syndrome samples, and an inverse linear correlation was seen between the level of miR-1244 and MEIS2 and UQCRB expression levels. Since many of computer-predicted miR-1244 target genes play roles in transcriptional regulation, overexpression of miR-1244 due to tetrasomy 12p may contribute to the pleiotropic phenotype of Pallister-Killian Syndrome by modulating its downstream target genes including MEIS2 and UQCRB .
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Pallister Killian Syndrome
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2014Co-Authors: Kosuke Izumi, Ian D KrantzAbstract:Pallister–Killian Syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS. © 2014 Wiley Periodicals, Inc.
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Cassidy and Allanson's Management of Genetic Syndromes - Pallister-Killian Syndrome.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2014Co-Authors: Kosuke Izumi, Ian D KrantzAbstract:Pallister–Killian Syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS. © 2014 Wiley Periodicals, Inc.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
PloS one, 2014Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Alisha Wilkens, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2.
Kosuke Izumi - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
2016Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Alisha B. Wilkens, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such a
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12p microRNA expression in fibroblast cell lines from probands with Pallister-Killian Syndrome
Chromosome Research, 2014Co-Authors: Kosuke Izumi, Zhe Zhang, Maninder Kaur, Ian D KrantzAbstract:Pallister-Killian Syndrome is a multisystem sporadic genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, seizures, diaphragmatic hernia, and other systemic abnormalities. Pallister-Killian Syndrome is typically caused by the presence of a supernumerary isochromosome that is always present in a tissue limited mosaic pattern, resulting in tetrasomy 12p due to the two extra copies of 12p. We evaluated the potential contribution of microRNAs located on 12p to the pathogenesis of Pallister-Killian Syndrome phenotype. Using skin fibroblast cell lines from 13 probands with Pallister-Killian Syndrome and 5 normal matched controls, the expression level of 5 microRNAs located on 12p and their target gene mRNA levels were measured. All measured micro RNAs located on 12p were overexpressed in Pallister-Killian Syndrome fibroblasts, although the fold difference of the expression level was lower than copy number differences. Among the five microRNAs, miR-1244 had the highest fold difference. Many of computer-predicted target genes of miR-1244 were downregulated in Pallister-Killian Syndrome skin fibroblasts. In particular, expression levels of MEIS2 and UQCRB were significantly decreased in Pallister-Killian Syndrome samples, and an inverse linear correlation was seen between the level of miR-1244 and MEIS2 and UQCRB expression levels. Since many of computer-predicted miR-1244 target genes play roles in transcriptional regulation, overexpression of miR-1244 due to tetrasomy 12p may contribute to the pleiotropic phenotype of Pallister-Killian Syndrome by modulating its downstream target genes including MEIS2 and UQCRB .
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Pallister Killian Syndrome
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2014Co-Authors: Kosuke Izumi, Ian D KrantzAbstract:Pallister–Killian Syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS. © 2014 Wiley Periodicals, Inc.
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Cassidy and Allanson's Management of Genetic Syndromes - Pallister-Killian Syndrome.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2014Co-Authors: Kosuke Izumi, Ian D KrantzAbstract:Pallister–Killian Syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS. © 2014 Wiley Periodicals, Inc.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
PloS one, 2014Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Alisha Wilkens, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2.
Alisha Wilkens - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
PloS one, 2014Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Alisha Wilkens, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2.
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Cardiac manifestations of Pallister–Killian Syndrome
American Journal of Medical Genetics Part A, 2014Co-Authors: Richard K. Tilton, Alisha Wilkens, Ian D Krantz, Kosuke IzumiAbstract:Pallister-Killian Syndrome (PKS) is a sporadic multisystem genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, differences in skin pigmentation, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. Although congenital heart defects have been described in association with PKS, the full spectrum of heart disease is still not entirely known. Here, we describe the pattern of cardiac findings of 81 probands with PKS who have had at least one cardiac evaluation, demonstrating structural heart difference in 37% of our cohort (n = 30). Septal defects such as atrial or ventricular septal defects (n = 12) were the most commonly seen congenital heart differences. Additional findings included the occasional occurrence of bicuspid aortic valve, aortic dilatation, and cardiac hypertrophy/cardiomyopathy. We suggest cardiac evaluation for all individuals with PKS at the time of diagnosis as well as subsequent longitudinal follow-up to monitor for the development of cardiomyopathy and aortic dilatation.
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Cardiac manifestations of Pallister-Killian Syndrome.
American journal of medical genetics. Part A, 2014Co-Authors: Richard K. Tilton, Alisha Wilkens, Ian D Krantz, Kosuke IzumiAbstract:Pallister-Killian Syndrome (PKS) is a sporadic multisystem genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, differences in skin pigmentation, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. Although congenital heart defects have been described in association with PKS, the full spectrum of heart disease is still not entirely known. Here, we describe the pattern of cardiac findings of 81 probands with PKS who have had at least one cardiac evaluation, demonstrating structural heart difference in 37% of our cohort (n = 30). Septal defects such as atrial or ventricular septal defects (n = 12) were the most commonly seen congenital heart differences. Additional findings included the occasional occurrence of bicuspid aortic valve, aortic dilatation, and cardiac hypertrophy/cardiomyopathy. We suggest cardiac evaluation for all individuals with PKS at the time of diagnosis as well as subsequent longitudinal follow-up to monitor for the development of cardiomyopathy and aortic dilatation.
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novel clinical manifestations in Pallister Killian Syndrome comprehensive evaluation of 59 affected individuals and review of previously reported cases
American Journal of Medical Genetics Part A, 2012Co-Authors: Alisha Wilkens, Kosuke Izumi, Anna Kostanecka, Hongbin Liu, Kristen Park, Marie Jackson, Mary Pipan, Phillip Pallister, Lindsey Campbell, Ian D KrantzAbstract:Pallister–Killian Syndrome is a rare, multi-system developmental diagnosis typically caused by tetrasomy of chromosome 12p that exhibits tissue-limited mosaicism. The spectrum of clinical manifestations in Pallister–Killian Syndrome is wide and includes craniofacial anomalies, clefts, ophthalmologic, audiologic, cardiac, musculoskeletal, diaphragmatic, gastrointestinal, genitourinary, and cutaneous anomalies in association with intellectual disability and seizures. Growth parameters are often normal to elevated at birth with deceleration of growth postnatally. No formal estimate of the prevalence of Pallister–Killian Syndrome has been made. Here, we report the clinical findings in 59 individuals with Pallister–Killian Syndrome who were ascertained at Pallister–Killian Syndrome Foundation family meetings held in the summers of 2006, 2008, 2009, and 2010. In addition, the clinical findings of 152 cases reported in the medical literature were reviewed and compared to the cohort examined here. Several novel clinical characteristics were identified through detailed dysmorphology examinations of this cohort and reassertion of a mild developmental variant is described. This report expands the clinical manifestations of Pallister –Killian Syndrome and highlights the variable expressivity of this diagnosis with important implications for diagnosis and counseling. 2012 Wiley Periodicals, Inc.
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Novel clinical manifestations in Pallister-Killian Syndrome: comprehensive evaluation of 59 affected individuals and review of previously reported cases.
American journal of medical genetics. Part A, 2012Co-Authors: Alisha Wilkens, Kosuke Izumi, Anna Kostanecka, Hongbin Liu, Kristen Park, Lindsey B Campbell, Marie Jackson, Mary Pipan, Phillip Pallister, Ian D KrantzAbstract:Pallister-Killian Syndrome is a rare, multi-system developmental diagnosis typically caused by tetrasomy of chromosome 12p that exhibits tissue-limited mosaicism. The spectrum of clinical manifestations in Pallister-Killian Syndrome is wide and includes craniofacial anomalies, clefts, ophthalmologic, audiologic, cardiac, musculoskeletal, diaphragmatic, gastrointestinal, genitourinary, and cutaneous anomalies in association with intellectual disability and seizures. Growth parameters are often normal to elevated at birth with deceleration of growth postnatally. No formal estimate of the prevalence of Pallister-Killian Syndrome has been made. Here, we report the clinical findings in 59 individuals with Pallister-Killian Syndrome who were ascertained at Pallister-Killian Syndrome Foundation family meetings held in the summers of 2006, 2008, 2009, and 2010. In addition, the clinical findings of 152 cases reported in the medical literature were reviewed and compared to the cohort examined here. Several novel clinical characteristics were identified through detailed dysmorphology examinations of this cohort and reassertion of a mild developmental variant is described. This report expands the clinical manifestations of Pallister-Killian Syndrome and highlights the variable expressivity of this diagnosis with important implications for diagnosis and counseling.
Laura K. Conlin - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
2016Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Alisha B. Wilkens, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such a
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Genome-Wide Expression Analysis in Fibroblast Cell Lines from Probands with Pallister Killian Syndrome
PloS one, 2014Co-Authors: Maninder Kaur, Kosuke Izumi, Zhe Zhang, Alisha Wilkens, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Ian D KrantzAbstract:Pallister Killian Syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian Syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian Syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian Syndrome probands and supportive evidence for a Pallister Killian Syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian Syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2.
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Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister-Killian Syndrome.
American journal of medical genetics. Part A, 2012Co-Authors: Laura K. Conlin, Kosuke Izumi, Maninder Kaur, Alisha Wilkens, Phillip Pallister, Lindsey Campbell, Dinah Clark, Matthew A Deardorff, Elaine H Zackai, Hakon HakonarsonAbstract:Identification of the isochromosome 12p (i(12p)) associated with Pallister-Killian Syndrome is complicated by the low frequency of this supernumerary chromosome in PHA stimulated peripheral blood lymphocytes, and frequently requires cytogenetic analysis of fibroblast cells. Recently, it has been shown that array CGH techniques are able to detect tetrasomy 12p in peripheral blood, even when not identified by traditional cytogenetic techniques. We studied 15 patients with a previous cytogenetic and clinical diagnosis of Pallister-Killian Syndrome using genome-wide SNP arrays to investigate the ability of this platform to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p in all samples from fibroblasts, but was only able to detect it in 46% of blood samples. The genotyping information available from the SNP arrays allowed for the detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin for the isochromosome in the majority of patients. Analysis of the percentage of abnormal cells with patient age at time of study suggests that the frequency of the i(12p) decreased with age in blood, but not in fibroblasts. These highlight the power of SNP arrays in detecting and characterizing the isochromosome 12p in Pallister-Killian Syndrome as well as underscoring the important utility of traditional cytogenetic techniques.
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Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister-Killian Syndrome.
American Journal of Medical Genetics Part A, 2012Co-Authors: Laura K. Conlin, Kosuke Izumi, Maninder Kaur, Alisha Wilkens, Phillip Pallister, Lindsey Campbell, Dinah Clark, Matthew A Deardorff, Elaine H Zackai, Hakon HakonarsonAbstract:Identification of the isochromosome 12p (i(12p)) associated with Pallister–Killian Syndrome is complicated by the low frequency of this supernumerary chromosome in PHA stimulated peripheral blood lymphocytes, and frequently requires cytogenetic analysis of fibroblast cells. Recently, it has been shown that array CGH techniques are able to detect tetrasomy 12p in peripheral blood, even when not identified by traditional cytogenetic techniques. We studied 15 patients with a previous cytogenetic and clinical diagnosis of Pallister–Killian Syndrome using genome-wide SNP arrays to investigate the ability of this platform to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p in all samples from fibroblasts, but was only able to detect it in 46% of blood samples. The genotyping information available from the SNP arrays allowed for the detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin for the isochromosome in the majority of patients. Analysis of the percentage of abnormal cells with patient age at time of study suggests that the frequency of the i(12p) decreased with age in blood, but not in fibroblasts. These highlight the power of SNP arrays in detecting and characterizing the isochromosome 12p in Pallister–Killian Syndrome as well as underscoring the important utility of traditional cytogenetic techniques. © 2012 Wiley Periodicals, Inc.
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Duplication 12p and Pallister-Killian Syndrome: a case report and review of the literature toward defining a Pallister-Killian Syndrome minimal critical region.
American journal of medical genetics. Part A, 2012Co-Authors: Kosuke Izumi, Alisha Wilkens, Nancy B. Spinner, Laura K. Conlin, Elaine H Zackai, Donna Berrodin, Christopher Fincher, Chad Haldeman-englert, Sulagna C Saitta, Ian D KrantzAbstract:Pallister-Killian Syndrome (PKS) is a multisystem sporadic genetic condition characterized by facial anomalies, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, pigmentary skin differences, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. PKS is typically caused by the presence of a supernumerary isochromosome composed of the short arms of chromosome 12 resulting in tetrasomy 12p, which is often present in a tissue limited mosaic state. The PKS phenotype has also often been observed in individuals with complete or partial duplications of 12p (trisomy 12p rather than tetrasomy 12p) as the result of an interstitial duplication or unbalanced translocation. We have identified a proposita with PKS who has two small de novo interstitial duplications of 12p which, along with a review of previously reported cases, has allowed us to define a minimum critical region for PKS.
David J Amor - One of the best experts on this subject based on the ideXlab platform.
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Pallister Killian Syndrome caused by mosaicism for a supernumerary ring chromosome 12p
American Journal of Medical Genetics Part A, 2009Co-Authors: Alison Yeung, David Francis, Olivia Giouzeppos, David J AmorAbstract:Pallister–Killian Syndrome (PKS) is a rare but distinctive chromosomal Syndrome distinguished by severe intellectual impairment, characteristic facial features, and variable structural anomalies. The characteristic cytogenetic abnormality in PKS is a supernumerary isochromosome 12p that confers mosaic tetrasomy. We describe a female child with PKS in whom tetrasomy 12p resulted from a supernumerary ring chromosome containing two copies of chromosome 12cen ! p13, a novel cytogenetic finding. The ring chromosome exhibited tissuelimited mosaicism, being absent in blood but detected in 38% of buccal mucosa cells and 41% of skin fibroblasts. Our patient demonstrated the typical dysmorphic characteristics of PKS, but her development was relatively advanced in comparison to children with isochromosome PKS. Her milder developmental phenotype may be attributable to differences in the mosaic distribution or the genomic content of the ring chromosome compared to mosaic isochromosome 12p. 2009 Wiley-Liss, Inc.
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Pallister-Killian Syndrome caused by mosaicism for a supernumerary ring chromosome 12p.
American journal of medical genetics. Part A, 2009Co-Authors: Alison Yeung, David Francis, Olivia Giouzeppos, David J AmorAbstract:Pallister-Killian Syndrome (PKS) is a rare but distinctive chromosomal Syndrome distinguished by severe intellectual impairment, characteristic facial features, and variable structural anomalies. The characteristic cytogenetic abnormality in PKS is a supernumerary isochromosome 12p that confers mosaic tetrasomy. We describe a female child with PKS in whom tetrasomy 12p resulted from a supernumerary ring chromosome containing two copies of chromosome 12cen --> p13, a novel cytogenetic finding. The ring chromosome exhibited tissue-limited mosaicism, being absent in blood but detected in 38% of buccal mucosa cells and 41% of skin fibroblasts. Our patient demonstrated the typical dysmorphic characteristics of PKS, but her development was relatively advanced in comparison to children with isochromosome PKS. Her milder developmental phenotype may be attributable to differences in the mosaic distribution or the genomic content of the ring chromosome compared to mosaic isochromosome 12p.