PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression

Teye, Emmanuel K.; Lu, Shasha; Chen, Fangyuan; Yang, Weizhong; Abraham, Thomas; Stairs, Douglas B.; Wang, Honggang; Yochum, Gregory S.; Pu, Jeffrey J.

doi:10.1038/s41598-021-98218-y

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…These >150 proteins include enzymes, adhesion molecules, receptors, and regulatory proteins of the immune system 4 . Recently, PIGN has been shown to also mediate protein quality control within ER, contributing to maintaining chromosomal stability 5,6 . Biallelic disease‐causing variants in genes involved in the GPI synthesis pathway have been associated with epilepsy, developmental delay (DD), intellectual disability (ID), hypotonia, and multiple congenital anomalies affecting different organs 2,7 …”

Section: Introductionmentioning

confidence: 99%

“…4 Recently, PIGN has been shown to also mediate protein quality control within ER, contributing to maintaining chromosomal stability. 5,6 Biallelic disease-causing variants in genes involved in the GPI synthesis pathway have been associated with epilepsy, developmental delay (DD), intellectual disability (ID), hypotonia, and multiple congenital anomalies affecting different organs. 2,7 Forty-three patients with PIGN diseases from 32 families with 42 unique PIGN variants, including 10…”

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confidence: 99%

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PIGNencephalopathy: Characterizing the epileptology

et al. 2022

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proteins include enzymes, adhesion molecules, receptors, and regulatory proteins of the immune system. 4 Recently, PIGN has been shown to also mediate protein quality control within ER, contributing to maintaining chromosomal stability. 5,6 Biallelic disease-causing variants in genes involved in the GPI synthesis pathway have been associated with epilepsy, developmental delay (DD), intellectual disability (ID), hypotonia, and multiple congenital anomalies affecting different organs. 2,7 Forty-three patients with PIGN diseases from 32 families with 42 unique PIGN variants, including 10

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

PIGNencephalopathy: Characterizing the epileptology

et al. 2022

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Congenital Aneuploidy in Klinefelter Syndrome with B-Cell Acute Lymphoblastic Leukemia Might Be Associated with Chromosomal Instability and Reduced Telomere Length

Kjeldsen

2022

Cancers

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Rare congenital aneuploid conditions such as trisomy 13, trisomy 18, trisomy 21 and Klinefelter syndrome (KS, 47,XXY) are associated with higher susceptibility to developing cancer compared with euploid genomes. Aneuploidy frequently co-exists with chromosomal instability, which can be viewed as a “vicious cycle” where aneuploidy potentiates chromosomal instability, leading to further karyotype diversity, and in turn, paving the adaptive evolution of cancer. However, the relationship between congenital aneuploidy per se and tumor initiation and/or progression is not well understood. We used G-banding analysis, array comparative genomic hybridization analysis and quantitative fluorescence in situ hybridization for telomere length analysis to characterize the leukemic blasts of a three-year-old boy with KS and B-cell acute lymphoblastic leukemia (B-ALL), to gain insight into genomic evolution mechanisms in congenital aneuploidy and leukemic development. We found chromosomal instability and a significant reduction in telomere length in leukemic blasts when compared with the non-leukemic aneuploid cells. Reviewing published cases with KS and B-ALL revealed 20 additional cases with B-ALL diagnostic cytogenetics. Including our present case, 67.7% (14/21) had acquired two or more additional chromosomal aberrations at B-ALL diagnosis. The presented data indicate that congenital aneuploidy in B-ALL might be associated with chromosomal instability, which may be fueled by enhanced telomere attrition.

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PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation

et al. 2022

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Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1. Materials and Methods: Next-generation sequencing (NGS) technology was used to identify the changes in the DNA sequence. Sanger sequencing of gDNA of probands and their parents was used for validation and segregation analysis. Bioinformatics tools were used to investigate the consequences of pathogenic or likely pathogenic PIGN variants at the protein sequence and structure level. Results: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G>T];[1247_1251del] PIGN genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T>G];[1674+1G>C] PIGN genotype in family 2. In silico, c.1942G>T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G>C (p.(Glu525AspfsTer68)) variants are predicted to result in a premature termination codon that leads to truncated and functionally disrupted protein causing the phenotype of MCAHS1 in the affected individuals. Conclusions: PIGN-related disease represents a wide spectrum of phenotypic features, making clinical diagnosis inaccurate and complicated. The genetic testing of every individual with this phenotype provides new insights into the origin and development of the disease.

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PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression

Cited by 3 publications

References 66 publications

PIGNencephalopathy: Characterizing the epileptology

PIGNencephalopathy: Characterizing the epileptology

Congenital Aneuploidy in Klinefelter Syndrome with B-Cell Acute Lymphoblastic Leukemia Might Be Associated with Chromosomal Instability and Reduced Telomere Length

PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation

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