Novel mutations of maternal effect gene thyroid hormone receptor interactor 13 involved in biparental complete...

Biparental complete hydatidiform mole (BiCHM) is a rare form of molar pregnancy, frequently associated with familial recurrence, whose mechanism was historically unclear. It is classically diploid with biparental inheritance, but manifests as a complete hydatidiform mole (CHM). Cytogenetic studies suggested a link to maternal mutations in imprinted genes NOD-like receptor family, pyrin domain containing 7 or Kelch helper domain containing 3-like within the oocyte. This case reports a novel gene association.

A 43-year-old woman presented with a history of recurrent abnormal pregnancies: 2 CHM and 1 spontaneous abortion following an intracytoplasmic sperm injection (ICSI)-assisted conception.

Short tandem repeat polymorphism analysis of products of conception (including both CHM and the aborted ICSI pregnancy) revealed all 3 were biparental triploids derived from the patient and her husband. Whole-exome sequencing of the patient's family identified that the patient carries compound heterozygous mutations (c.-82G > A [paternally inherited] and c.*106G > A [maternally inherited]) in the autosomal recessive gene thyroid hormone receptor interactor 13 (TRIP13), confirmed by Sanger sequencing.

Given the genetic findings and history of recurrent BiCHM, ovarian donation or adoption was recommended as the treatment strategy to achieve a normal pregnancy.

The genetic diagnosis was established, informing future reproductive counseling and management options.

To our knowledge, this is the first report linking biallelic TRIP13 mutations to recurrent BiCHM, indicating its potential role in the pathogenesis. ICSI-assisted reproduction did not improve pregnancy outcomes. Ovarian donation or adoption was recommended.