Mutations in the gene encoding the α-subunit of the G_s protein in molar pregnancy

Abstract

Molar pregnancy is a gestational trophoblastic disease associated with a trophoblastic proliferation and a protein synthesis alteration. It is characterized by the presence of hydatiform moles, which are fluid-filled cysts derived from the chorionic villi of the placenta. Recent studies have reported a reduced expression of several types of G proteins including G_sα in molar pregnancies suggesting alterations in G protein structure in hydatiform moles. To identify mutations that lead to G_sα deficiency, we isolated genomic DNA from hydatiform moles and used polymerase chain reaction to amplify all exons of the G_sα gene. Amplified G_sα gene fragments were analyzed by sequencing using the dideoxy chain termination method. Tissues obtained from three complete hydatiform moles and one partial hydatiform mole were examined. We have identified a heterozygous 8-bp deletion in exon 10 of the G_sα gene, in two complete hydatiform moles, that had evidence for a dysfunctional G_sα protein. This deletion produced a truncated protein. We have also identified a heterozygous polymorphism in exon 5 in two complete hydatiform moles, and a homozygous substitution (A→G) in intron 5 of the G_sα gene in the other complete hydatiform mole; these two last types of mutations should not have any effects on protein activity.