Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Case report a novel KERA mutation associated with cornea plana and its predicted effect on protein function

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Knowledge about hereditary nonpolyposis colorectal cancer; mutation carriers and physicians at equal levels

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. upd(20)mat is a rare cause of the Silver-Russell-syndrome-like phenotype: Two unrelated cases and screening of large cohorts

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Distribution of risk alleles in patients with age-related macular degeneration

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Chromothripsis and DNA Repair Disorders

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

BACKGROUND: Transient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1 and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers.

METHODS: Genome-wide DNA methylation analysis was performed on four individuals with homozygous or compound heterozygous ZFP57 mutations, three relatives with heterozygous ZFP57 mutations and five controls. Methylation status of selected regions showing aberrant methylation in the patients was verified using bisulfite-sequencing.

RESULTS: We found large variability among the patients concerning the number and identity of the differentially methylated regions, but more than 60 regions were aberrantly methylated in two or more patients and a novel region within PPP1R13L was found to be hypomethylated in all the patients. The hypomethylated regions in common between the patients are enriched for the ZFP57 DNA binding motif.

CONCLUSIONS: We have expanded the epimutational spectrum of TNDM1 associated with ZFP57 mutations and found one novel region within PPP1R13L which is hypomethylated in all TNDM1 patients included in this study. Functional studies of the locus might provide further insight into the etiology of the disease.

OriginalsprogEngelsk
TidsskriftBMC Medical Genetics
Vol/bind17
Sider (fra-til)29
DOI
StatusUdgivet - 2016

ID: 46437662