A homozygous missense mutation of the GUSB gene leads to mucopolysaccharidosis type VII identification in a family with twice adverse pregnancy outcomes due to non-immune hydrops fetalis.

Non-immune hydrops fetalis (NIHF) is a common and severe manifestation of many genetic disorders. The ultrasound is an ideal method for diagnosing hydrops fetalis during pregnancy. Since most NIHFs do not have an identifiable cause, determining the underlying etiology remains a challenge for prenatal counseling. Due to advancements in exome sequencing, the diagnostic rates of NIHF have recently increased. As reported here, DNA was extracted from the amniotic fluid of a pregnant woman who was prenatally diagnosed with a NIHF type of unclear origin. Amniocentesis sampling demonstrated a normal female karyotype and copy number variation(CNVs) without alterations. Tri-whole exome sequencing (WES) was conducted to identify possible causative variants. In the fetus, a genetic mutation was identified as a homozygous form. The mutation was located on the glucuronidase beta (GUSB) gene: NM_000181.3: c.1324G > A; p. Ala442Thr; Chr7:65439349, which leads to mucopolysaccharidosis type VII. This mutation was inherited from the parents and was first reported to be related to NIHF. We conclude that the use of WES is beneficial for NIHF cases whose prognosis has not been explained by standard genetic testing.