The Critical Role of Prenatal Genetic Study in Prevention of Primary Immunodeficiency in High-risk Families: The Largest Report of 107 Cases
Prenatal Diagnosis of Primary Immunodeficiency Disorders
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.
2. Sponzilli I, Notarangelo LD. Severe Combined Immunodeficiency (SCID): from molecular basisto clinical management. Acta Biomed. 2010;82(1):5-13.
3. Ameratunga R, Woon S-T, Neas K, Love DR. The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review. Allergy Asthma Clin Immunol. 2010;6(1):12.
4. Abraham RS. Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies. Clin Mol Allergy. 2011;9(1):6.
5. Modell V, Gee B, Lewis DB, Orange JS, Roifman CM, Routes JM, et al. Global study of primary immunodeficiency diseases (PI)—diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. Immunol Res. 2011;51(1):61.
6. Derpoorter C, Bordon V, Laureys G, Haerynck F, Lammens T. Genes at the Crossroad of Primary Immunodeficiencies and Cancer. Front Immunol. 2018;9:2544.
7. Ayşe M, Dirk R. Prenatal diagnosis of chronic granulomatous disease in a male fetus. Iranian J Allergy Asthma Immunol. 2009;8(1):57-61.
8. Ariga T, Iwamura M, Miyakawa T, Takahashi H, Mikami A, Sakiyama Y. Prenatal diagnosis of the Wiskott–Aldrich syndrome by PCR‐based methods. Pediatr Int. 2001;43(6):716-9.
9. Madkaikar MR, Gupta M, Rao M, Ghosh K. Prenatal diagnosis of LAD-I on cord blood by flowcytometry. Indian J Pediatr. 2012;79(12):1605-9.
10. Wah YM, Leung TY, Cheng YKY, Sahota DS. Procedure-Related Fetal Loss following Chorionic Villus Sampling after First-Trimester Aneuploidy Screening. Fetal Diagn Ther. 2017;41(3):184-90.
11. Wessels T-M, Krause A. Genetic counselling in primary immunodeficiency disorders. Current Allergy & Clinical Immunology. 2012;25(4):199-203.
12. Tabori U, Mark Z, Amariglio N, Etzioni A, Golan H, Biloray B, et al. Detection of RAG mutations and prenatal diagnosis in families presenting with either T–B–severe combined immunodeficiency or Omenn's syndrome. Clini Genet. 2004;65(4):322-6.
13. Nadkarni A, Hariharan P. Molecular Techniques for Prenatal Diagnosis. Hematopathology: Advances in Understanding. 2019:469.
14. E. Richard Stiehm HDO, Jerry A. Winklestein. Part II (Primary Immunodeficiencies). Immunologic Disorders in Infants and Children2004. p. 289-355.
15. Saadat M, Ansari-Lari M, Farhud D. Short report consanguineous marriage in Iran. Ann Hum Biol. 2004;31(2):263-9.
16. DiSanto JP, Markiewicz S, Gauchat J-F, Bonnefoy J-Y, Fischer A, de Saint Basile G. Prenatal diagnosis of X-linked hyper-IgM syndrome. N Engl J Med. 1994;330(14):969-73.
17. Weening R, Bredius R, Wolf H, Van der Schoot C. Prenatal diagnostic procedure for leukocyte adhesion deficiency. Prenat Diagn. 1991;11(3):193-7.
18. Akolekar R, Beta J, Picciarelli G, Ogilvie C, d'Antonio F. Procedure‐related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta‐analysis. Ultrasound Obstet Gynecol. 2015;45(1):16-26.
19. Alfirevic Z, Navaratnam K, Mujezinovic F. Amniocentesis and chorionic villus sampling for prenatal diagnosis. The Cochrane Library. 2017.
20. Esmaeili B, Ghadami M, Fazlollahi MR, Niroomanesh S, Atarod L, Chavoshzadeh Z, et al. Prenatal diagnosis of leukocyte adhesion deficiency type-1 (five cases from iran with two new mutations). Iranian J Allergy Asthma Immunol. 2014;13(1):61-5.
21. Mishra A, Gupta M, Dalvi A, Ghosh K, Madkaikar M. Rapid Flow cytometric prenatal diagnosis of primary immunodeficiency (PID) disorders. J Clin Immunol. 2014;34(3):316-22.
22. Curtis MG, Walker B, Denny TN. Flow cytometric methods for prenatal and neonatal diagnosis. J Immunol Methods. 2011;363(2):198-209.
23. Winkelstein JA, Marino MC, Johnston Jr RB, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine. 2000;79(3):155-69.
24. Richardson M, Ayliffe M, Helbert M, Davies E. A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test. J Immunol Methods. 1998;219(1):187-93.
25. Kulkarni M, Gupta M, Madkaikar M. Phenotypic Prenatal Diagnosis of Chronic Granulomatous Disease: A Useful Tool in The Absence Of Molecular Diagnosis. Scand J Immunol. 2017;86(6):486-90.
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