PROZ and ARNT genes novel homozygous mutations are related to recurrent pregnancy loss: case report of 2 cases

Background Recurrent miscarriage (RM) or recurrent pregnancy loss (RPL) is a complex situation, characterized by two, three, or more pregnancy losses. The normal progression of pregnancy relies heavily on the proper functioning of the PROZ and ARNT genes, and their partial or complete deficiencies will result in early pregnancy loss and also recurrent pregnancy losses. Methods Present study aims to find PROZ and ARNT novel mutations as causes of RPL; and involves two couples that had a consanguineous marriage and were referred with three recurring miscarriages. Pathological tests were requested for the fetus, and high-resolution Giemsa banding karyotypes were requested for the couple to determine the cause. Abortion samples were also used for array CGH and whole-exome sequencing to analyze mutations. Confirming the mutation involved conducting Sanger sequencing, which is noteworthy. Results Based on the results, our first proband has a novel likely pathogenic homozygous mutation NM_003891:c.349T > C (p.Y117H) in the PROZ gene located on 13q34 as a novel mutation of the PROZ gene, and our second proband has a novel likely pathogenic homozygous mutation NM_001286035:exon16:c.1353-2A > G in the ARNT gene, located on 1q21.3. Sanger sequencing confirmed homozygosity of these two mutations in the probands and heterozygosity of these loci in their parents, suggesting them as likely pathogenic mutations and an autosomal recessive inheritance pattern in RPL. Conclusion Novel likely pathogenic homozygous mutation NM_003891:c.349T > C (p.Y117H) in PROZ gene, and novel likely pathogenic homozygous mutation in ARNT gene may be related to RPL.