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| Status |
Public on Jun 27, 2018 |
| Title |
Patients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalities. |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Kabuki syndrome is a monogenic disorder caused by loss of function variants in either of two genes encoding histone-modifying enzymes. We performed targeted sequencing in a cohort of 27 probands with a clinical diagnosis of Kabuki syndrome. Of these, 12 had causative variants in the two known Kabuki syndrome genes. In 2, we identified presumptive loss of function de novo variants in KMT2A (missense and splice site variants), a gene that encodes another histone modifying enzyme previously exclusively associated with Wiedermann-Steiner syndrome. Although Kabuki syndrome is a disorder of histone modification, we also find alterations in DNA methylation among individuals with a Kabuki syndrome diagnosis relative to matched normal controls, regardless of whether they carry a variant in KMT2A or KMT2D or not. Furthermore, we observed characteristic global abnormalities of DNA methylation that distinguished patients with a loss of function variant in KMT2D or missense or splice site variants in either KMT2D or KMT2A from normal controls. Our results provide new insights into the relationship of genotype to epigenotype and phenotype and indicate cross-talk between histone and DNA methylation machineries exposed by inborn errors of the epigenetic apparatus.
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| Overall design |
Case-control design. 48 total samples (randomized across four 12-well BeadChips): 4 synthetic methylation controls, 6 parental controls, 9 age-matched controls, 27 probands with a Kabuki Syndrome phenotype, and 2 patients originally recruited from the same clinic but dropped from further analysis when they were found to not have KS
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| Contributor(s) |
Brucato MF, Sobreira N, Zhang L, Ladd-Acosta C, Ongaco C, Romm J, Doheny KF, Mingroni-Netto RC, Bertola D, Kim CA, Perez AB, Melaragno MI, Valle D, Meloni VA, Bjornsson HT |
| Citation(s) |
29255178 |
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| Submission date |
Jun 26, 2018 |
| Last update date |
Jun 28, 2023 |
| Contact name |
Hans Tomas Bjornsson |
| E-mail(s) |
[email protected]
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| Organization name |
Johns Hopkins University School of Medicine
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| Department |
McKusick-Nathans Institute of Genetic Medicine
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| Street address |
733 N. Broadway
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA478052 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116300_18.05.30.for.GEO.processed.M.values.txt.gz |
99.5 Mb |
(ftp)(http) |
TXT |
| GSE116300_18.05.30.for.GEO.processed.beta.values.txt.gz |
90.0 Mb |
(ftp)(http) |
TXT |
| GSE116300_RAW.tar |
539.1 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data are available on Series record |
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