Individuals with monogenic diabetes caused by inactivating glucokinase (GCK) variations do not usually require treatment, save maybe during pregnancy. The fetal GCK genotype dictates whether therapy is necessary throughout pregnancy, although noninvasive techniques are not clinically accessible. The goal of this research is to provide a non-invasive technique for determining fetal GCK genotype from maternal cell-free fetal DNA. This was a proof-of-concept research involving three pregnant women with a causal GCK mutation that employed data from 1) large parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) paternal genotypes to calculate the relative haplotype dosage of the pathogenic variant-linked haplotype. A sequential probability ratio test was used to conduct statistical testing of variant inheritance (SPRT). Plasma cell-free DNA was collected once between gestational weeks 24 and 36 in each of the three instances. The fetal percentage of cell-free DNA varied between 21.8 and 23.0 percent. In cell-free DNA, paternal homozygous alleles that were similar to the maternal GCK variant-linked allele were not overrepresented. Paternal homozygous alleles were considerably overrepresented if they were similar to the maternal wild-type–linked allele. Researchers expected that all three situations would not inherit the GCK variation based on the SPRT. In each case, postnatal baby genotyping verified our hypothesis.

They effectively used cell-free DNA to predict fetal GCK genotype in three pregnant women who had an inactivating GCK variation. This approach might help customize hyperglycemia therapy in women with GCK monogenic diabetes who are pregnant.

 

Reference: https://academic.oup.com/jcem/article-abstract/106/9/2678/6241945?redirectedFrom=fulltext