PROZ and ARNT genes novel homozygous mutations are related to Recurrent pregnancy loss

Abstract Background Recurrent miscarriage or Recurrent pregnancy loss is a complex situation, defined by two, three or more pregnancy losses. Expression of PROZ and ARNT genes are vital in normal pregnancy and their partial or complete deficiencies will result in early pregnancy loss and also recurrent pregnancy losses. Present study aims to find PROZ and ARNT novel mutations as causes of Recurrent miscarriage; and involves two couples that they had a consanguineous marriage and referred with 3 Recurring miscarriages. To find out the cause, pathological tests were requested for fetus and high resolution giemsa banding karyotypes were requested for couple. Also product of abortion sampling was done for array CGH and whole-exome sequencing in order to mutation analysis. It is notable that sanger sequencing was done for confirming the mutation. Results Based on the results, our first proband has novel likely pathogenic homozygous mutation NM_003891:c.349T > C (p.Y117H) in PROZ gene locates on 13q34 as a novel mutation of the PROZ gene, and our second proband has novel likely pathogenic homozygous mutation NM_001286035:exon16:c.1353-2A > G in ARNT gene, locates on 1q21.3. Sanger sequencing confirmed homozygosity of these two mutations in the probands and heterozygosity of these loci in their parents, suggesting it as the likely pathogen mutations, and autosomal recessive inheritance pattern in Recurrent miscarriage. 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 are related to Recurrent miscarriage.