Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Abstract

Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother’s health. WES after the birth of the twins confirmed the molecular data.

Identification of SOX18 as a New Gene Predisposing to Congenital Heart Disease

“…The constructed whole-exome library was captured using the SureSelect Human All Exon V6 kit (Agilent Technologies, Santa Clara, CA, USA) and sequenced under the HiSeq 2000 platform (Illumina, San Diego, CA, USA), as per the manufacturer’s protocol. Bioinformatical assay of the datasets produced by whole-exome sequencing (WES, New York, NY, USA) was conducted as described elsewhere [ 81 , 82 , 83 , 84 ]. Sanger sequencing was conducted to validate the candidate variations discovered by WES and bioinformatical analysis.…”

Benign Recurrent Intrahepatic Cholestasis: Where Are We Now?

“…BRIC1 can present with pancreatitis, diarrhea, and hearing loss, attributed to the expression of mutated ATP8B1 in the pancreas, intestines, and cochlear cells, respectively. Cholelithiasis has been reported in BRIC2 [33,[45][46][47][48].…”

“…Table 1 provides details on BRIC cases and their characteristics over the past decade. Liver biopsy abnormalities are observed only during the attacks, with intrahepatic cholestasis resolving during asymptomatic intervals [33,[45][46][47][48]. A distinctive feature is the absence of progression to cirrhosis, setting BRIC apart from PFIC.…”

Benign Recurrent Intrahepatic Cholestasis: Where are we now?

“…BRIC-1 can present with pancreatitis, diarrhea, and hearing loss, attributed to the expression of mutated ATP8B1 in the pancreas, intestines, and cochlear cells, respectively. Cholelithiasis has been reported in BRIC-2 [27,[39][40][41][42].…”

“…Table 1 provides details on BRIC cases and their characteristics over the past decade. Liver biopsy abnormalities are observed only during the attacks, with intrahepatic cholestasis resolving during asymptomatic intervals [27,[39][40][41][42]. A distinctive feature is the absence of progression to cirrhosis, setting BRIC apart from PFIC.…”