Article Text
Abstract
Background ZNF597, encoding a zinc-finger protein, is the human-specific maternally expressed imprinted gene located on 16p13.3. The parent-of-origin expression of ZNF597 is regulated by the ZNF597:TSS-DMR, of which only the paternal allele acquires methylation during postimplantation period. Overexpression of ZNF597 may contribute to some of the phenotypes associated with maternal uniparental disomy of chromosome 16 (UPD(16)mat), and some patients with UPD(16)mat presenting with Silver-Russell syndrome (SRS) phenotype have recently been reported.
Methods A 6-year-old boy presented with prenatal growth restriction, macrocephaly at birth, forehead protrusion in infancy and clinodactyly of the fifth finger. Methylation, expression, microsatellite marker, single nucleotide polymorphism array and trio whole-exome sequencing analyses were conducted.
Results Isolated hypomethylation of the ZNF597:TSS-DMR and subsequent loss of imprinting and overexpression of ZNF597 were confirmed in the patient. Epigenetic alterations, such as UPD including UPD(16)mat and other methylation defects, were excluded. Pathogenic sequence or copy number variants affecting his phenotypes were not identified, indicating that primary epimutation occurred postzygotically.
Conclusion We report the first case of isolated ZNF597 imprinting defect, showing phenotypic overlap with SRS despite not satisfying the clinical SRS criteria. A novel imprinting disorder entity involving the ZNF597 imprinted domain can be speculated.
- DNA methylation
- genetics, medical
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Footnotes
Contributors KY designed and coordinated the study and drafted the manuscript. KY, TI, MN, AN and KM performed molecular analysis. YS, TN and HY provided detailed clinical data and materials for molecular analysis. KK, HF and KE provided normal control samples. KN, KH, TM, TO and MK supervised the study. All authors read and reviewed the manuscript.
Funding This work was supported by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (16H05362), a Grant-in-Aid for Clinical Research from the National Hospital Organization (H29-NHO(SEIIKU)−01), a Grant from the Takeda Science Foundation, a Grant from the Yamaguchi Endocrine Research Foundation, a Grant from the Foundation for Growth Science, a Grant from the Japanese Society for Pediatric Endocrinology and a donation from the Enomoto Children’s Clinic.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.