Gene mutations responsible for primary immunodeficiency disorders: A report from the first primary immunodeficiency biobank in Iran

Abstract

BackgroundPrimary immunodeficiency (PID) is a heterogeneous group of inheritable genetic disorders with increased susceptibility to infections, autoimmunity, uncontrolled inflammation and malignancy. Timely precise diagnosis of these patients is very essential since they may not be able to live with their congenital immunity defects; otherwise, they could survive with appropriate treatment. DNA biobanks of such patients could be used for molecular and genetic testing, facilitating the detection of underlying mutations in known genes as well as the discovery of novel genes and pathways.MethodsAccording to the last update of the International Union of Immunological Societies (IUIS) classification, patients are registered in our biobank during a period of 15 years. All patients’ data were collected via questionnaire and their blood samples were taken in order to extract and protect their DNA content.ResultsOur study comprised 197 patients diagnosed with PID. Antibody deficiency in 50 patients (25.4%), phagocytic defect in 47 patients (23.8%) and combined immunodeficiency with associated/syndromic feature in 19 patients (9.6%) were the most common PID diagnoses, respectively. The most common variant of PID in our study is common variable immunodeficiency, which accounted for 20 cases (10.1%), followed by chronic mucocutaneous candidiasis in 15 patients (7.9%) and congenital neutropenia in 13 patients (7%). Mean age at onset of disease was 4 years and mean age of diagnosis was 9.6 years. The average diagnostic delay was 5.5 years, with a range of 6 months to 46 years. Parental consanguinity and history of PID in family were observed in 70.2 and 48.9% of the patients, respectively. The majority of PID patients (93.3%) were from families with low socioeconomic status.ConclusionThis prospective study was designed to establish a PID Biobank in order to have a high quality DNA reservoir of these patients, shareable for international diagnostic and therapeutic collaborations. This article emphasizes the need to raise the awareness of society and general practitioners to achieve timely diagnosis of these patients and prevent current mismanagements.

Primary Immunodeficiencies in Russia: Data From the National Registry

“…In highly consanguineous populations, AR PIDs represent 70-90% of cases (32,33). Interestingly-though the Russian population is very heterogeneous, with low numbers of consanguineous marriages (45 families, 1.9%)-AR genetic defects comprised 30% of all defects described in the cohort, with 40% of these being homozygous for the respective mutations.…”

Chronic granulomatous disease presenting at age 52 with fulminant mulch pneumonitis

“…Although some large deletions of NCF1 have been reported in databases (the Human Gene Mutation Database and the University of California Santa Cruz Genome Browser), these seem to extend into adjacent genes, and the few published cases reporting similar deletions do not describe the associated patient phenotypes. 3 , 4 Thus, our case appears to be the first report of a clinical presentation associated with an NCF1 deletion including almost the entire gene. Because the patient did not have any children and his parents were deceased, a family genetic investigation was performed only on his 2 healthy sisters.…”

Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features

“…Considering the death of her parents shortly after the patient and the unavailability of the father’s clinical information and the DNA samples of the parents, it is not possible to investigate whether she was born in a consanguineous union with a WAS-mutated father be partnered with a WAS carrier. Although it may seem like only about 20% of the syndromic CIDs (11 out of 60 causative genes) are addressed in this study, the mentioned categories, especially ATM and DNMT3B/ZBTB24 , are the most common disorders identified in previous reports of CIDs with associated or syndromic features ( 11 , 33 , 34 ). Noteworthily, more than half of our patients are ATM deficient, and the frequency is quite skewed, which is different from worldwide frequency.…”