The Role of Monogenic Factors in Recurrent Pregnancy Loss in Iraqi Consanguineous Family with Variant Identifications by Couple whole Exome Sequencing Test

Abstract

Miscarriages occur in 15% of clinically identified pregnancies. At least two pregnancy losses constitute recurrent miscarriage (RM), which affects 1% to 5% of couples seeking to conceive. Both the genetic makeup and clinical presentation of RM are extremely varied. This research included 10 RM couples. Samples were taken from October 2021 to November 2022. Whole Exome Sequencing was used to identify the unknown genetic factors responsible for RM in tenth couples. The analysis of the carrier test determined a rare recurrent pregnancy loss associated with the autosomal recessive mutation. In addition, most of these cases were associated with close relative marriage. This type of pregnancy loss occurs in women, whose hormone level, ultrasound, and biochemical test reports were normal. Thisstudy identified thirteen pathogenic variants (PAH, ETHE1, BTD, GJB2, FOX3, HBA2, CYP21A2, NAGA, TBCE, PKHD1, FKBP10, ASPA, PLA2G6), seven likely pathogenic variants (FRAS1, NAGLU, PIEZO, DDHD2, TRIP4, CTU2, AGRN), and one VUS in FUT8 gene, in the autosomal recessive genes using WES. However, both patients and partners have altered variants in 20% ETHE1 genes; 15% FOX3; 10% of ASPA, DDHD2, PIEZO1, PKHD1, FUT8, and PAH. The detected mutations linked to multisystem abnormalities, neurodevelopmental disorders, cardiac malformations, skeletal dysplasia, metabolic disorders and renal diseases, fetal development during pregnancy, and recurrent miscarriage.