0000000001110132

AUTHOR

Maria Vittoria Cubellis

Additional file 9 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 9: Table S5. Primers used for pyrosequencing analysis.

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Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2

The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces t…

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Additional file 2 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 2: Figure S1. Pyrosequencing analysis of seven imprinted DMRs.

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Additional file 3 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 3 Figure S2. Batch effect adjustment of array datasets.

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Additional file 11 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 11: Table S7. Primers for Sanger sequencing validation.

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Additional file 10 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 10: Table S6. Sex and age information of controls of methylome analysis.

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Additional file 4 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 4: Figure S3. Violin plots showing whole-genome DNA methylation profiles of probands, their siblings and mothers, and 12 controls.

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Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Abstract Background PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established. Results We have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprintin…

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Additional file 7 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 7: Figure S4. Sanger sequencing validating the PADI6 variants identified by WES.

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Additional file 6 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 6: Table S3. Maternal genetic variants in homozigosity or compound heterozigosity identified by WES.

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Additional file 5 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 5: Table S2. Methylation defects of imprinted DMRs in patients affected by BWS-MLID whose mothers are carriers of loss of function mutations in PADI6.

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Additional file 1 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 1: Table S1. Pathogenic variants of PADI6 and corresponding clinical phenotype.

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Additional file 8 of Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance

Additional file 8: Table S4 . List of the maternal-effect gene variants associated with MLID in the offspring identified so far and corresponding clinical phenotype.

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