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Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome.

Authors :
Kazuki Yamazawa
Takanobu Inoue
Yoshihiro Sakemi
Toshinori Nakashima
Hironori Yamashita
Kaduki Khono
Hideki Fujita
Keisuke Enomoto
Kazuhiko Nakabayashi
Kenichiro Hata
Moeko Nakashima
Tatsuo Matsunaga
Akie Nakamura
Keiko Matsubara
Tsutomu Ogata
Masayo Kagami
Source :
Journal of Medical Genetics; Jun2021, Vol. 58 Issue 6, p427-432, 6p
Publication Year :
2021

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00222593
Volume :
58
Issue :
6
Database :
Complementary Index
Journal :
Journal of Medical Genetics
Publication Type :
Academic Journal
Accession number :
150460863
Full Text :
https://doi.org/10.1136/jmedgenet-2020-107019