Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene

Abstract

Aims: A couple were referred for prenatal genetic testing at 31 weeks' gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and a small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. Materials and Methods:Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid.Results: A pathogenic homozygous nonsense variant in KLHL7 (NM_001031710.2) associated with PERCHING syndrome (#617055) was identified. Conclusion:Whilst there are detailed descriptions of the many postnatal phenotypes seen in these patients, there are few reports of features identified during pregnancy. This report is the first published prenatal diagnosis of PERCHING syndrome and provides further information on the associated fetal phenotypes.

Facilitating variant curation sharing for fetal precision genomics: A new venture for prenatal diagnosis

“…We will consider publishing variants of uncertain significance (VUS) if they are a very close fit to the phenotype and need minimal additional evidence to allow conferring of P/LP status. The format of these short papers, designated as Fetal Phenotype‐Genotype Report , are illustrated in the reports by Kurolap 10 and Horton‐Bell 11 and their colleagues published in this issue. Instructions can be found in the instructions for authors (https://obgyn.onlinelibrary.wiley.com/hub/journal/10970223/about/author-guidelines).…”