The Critical Role of Prenatal Genetic Study in Prevention of Primary Immunodeficiency in High-risk Families: The Largest Report of 107 Cases

Abstract

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases.

Benefits, challenges and prospects of newborn screening for primary immunodeficiency

“…Meanwhile, there are lots of diseases which currently have no effective treatments and lead to fatal consequences in the first years of life 40 . Therefore, prenatal diagnosis in families with a history of PID remains an important area 42 .…”

A Low-Cost, High-Fidelity Simulator for Transabdominal Chorionic Villus Sampling

“…Chorionic villus sampling (CVS) remains an essential tool for first-trimester genetic diagnosis. This is especially true in pregnancies at risk for of single-gene disorders [1][2][3][4][5][6], those with high-risk aneuploidy screening results [2,7], or when abnormalities are detected on first-trimester ultrasound [2,[8][9][10][11]. While overall rates of invasive prenatal diagnostic procedures are decreasing, CVS makes up a greater proportion of invasive diagnostic procedures than in the past [3,12].…”