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.

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.

Effects of stent implantation for peripheral pulmonary artery stenosis on pulmonary vascular hemodynamics and right ventricular function in a patient with repaired tetralogy of Fallot.

Stent implantation is an effective alternative to surgery and balloon angioplasty for the treatment of stenotic vascular lesions. However, there is concern about the hemodynamic consequences related to the loss of vascular elasticity caused by the non-compliant property of the implanted stent. Here we report data for pulmonary vascular impedance and right ventricular performance after implantation of balloon-expanded stents for peripheral pulmonary stenosis in a 13-year-old girl with repaired pulmonary atresia and ventricular septal defect. Stent implantation reduced total vascular resistance, low-frequency impedance and wave reflection, and improved right ventricular contractile performance measured by the pressure-area relationship. However, pulmonary vascular wall stiffness remained elevated after stenting, and it was suggested that stent implantation resulted in a net increase in vascular wall stiffness. The long-term effects of implanted stents on vascular and ventricular hemodynamics need to be clarified.