Biallelic ANGPT2 loss-of-function causes severe early-onset non-immune hydrops fetalis.

ABSTRACT:

Background

Hydrops fetalis, a pathological fluid accumulation in two or more body compartments, is aetiologically heterogeneous. We investigated a consanguineous family with recurrent pregnancy loss due to severe early-onset non-immune hydrops fetalis.

Methods and results

Whole exome sequencing in four fetuses with hydrops fetalis revealed that they were homozygous for the angiopoietin-2 (ANGPT2) variant Chr8 (GRCh37/Hg19): 6385085T>C, NM_001147.2:c.557A>G. The substitution introduces a cryptic, exonic splice site predicted to result in loss of 10 nucleotides with subsequent shift in reading frame, leading to a premature stop codon. RNA analysis in the heterozygous parents demonstrated loss of detectable mutant allele, indicative of loss-of-function via nonsense-media

SUBMITTER: Smeland MF 

PROVIDER: S-EPMC9811075 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature