Clinical, Immunological and Genetic Findings of a Large Tunisian Series of Major Histocompatibility Complex Class II Deficiency Patients

Ben‐Mustapha, Imen; Ben-Farhat, Khaoula; Dhouib, Naouel Guirat; Dhemaied, Emna; Larguèche, Beya; Ben-Ali, Meriem; Chemli, J.; Bouguila, Jihéne; Ben-Mansour, Lamia; Mellouli, Fethi; Khémiri, M.; Béjaoui, Mohamed; Barbouche, Mohamed‐Ridha

doi:10.1007/s10875-013-9863-8

Cited by 38 publications

(32 citation statements)

References 24 publications

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“…The patterns of founder mutation distribution disclosed two types: those that are shared with other populations particularly from the North-African countries and those that are specific to Tunisia. One of the most illustrative PIDs examples for a regional founder effect is the AR MHC class II combined immunodeficiency that has been considered to be a “North-African disease.” Indeed, we have identified a founder effect for the highly frequent c.338-25_338del26 mutation (also known as 752delG-25) in the RFXANK gene resulting in a 26-bp deletion (31) that has been reported in other North-African studies (4, 5, 48). The founder event responsible for this mutation has been estimated to have arise approximately 2,250 years ago (12), a period concurrent to the Berber civilization.…”

Section: Investigations Of Homozygosity Mapping and Age Estimation Ofmentioning

confidence: 51%

“…The deeply rooted tradition of parental consanguinity in the Tunisian general population, which remained relatively constant during the last four decades (28), has resulted in an elevated burden of AR PIDs since consanguinity favors the expression of recessive alleles (29). This is the case for two otherwise rare AR PIDs, namely, MHC class II deficiency and LAD I, diagnosed in fewer than 200 and 300 patients worldwide (12, 30) but accounting for 56 and 30 patients in Tunisia, respectively (31, 32). One practical implication related to this high frequency is to recommend, at least for the MHC class II deficiency, routine investigation of DR expression for North-African patients presenting symptoms suggestive of combined deficiency.…”

Section: Molecular Studies and Mode Of Inheritancementioning

confidence: 99%

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Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly Consanguineous Population

et al. 2017

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During the last decades, the study of primary immunodeficiencies (PIDs) has contributed tremendously to unravel novel pathways involved in a variety of immune responses. Many of these PIDs have an autosomal recessive (AR) mode of inheritance. Thus, the investigation of the molecular basis of PIDs is particularly relevant in consanguineous populations from Middle East and North Africa (MENA). Although significant efforts have been made in recent years to develop genetic testing across the MENA region, few comprehensive studies reporting molecular basis of PIDs in these settings are available. Herein, we review genetic characteristics of PIDs identified in 168 patients from an inbred Tunisian population. A spectrum of 25 genes involved was analyzed. We show that AR forms compared to X-linked or autosomal dominant forms are clearly the most frequent. Furthermore, the study of informative consanguineous families did allow the identification of a novel hyper-IgE syndrome linked to phosphoglucomutase 3 mutations. We did also report a novel form of autoimmune lymphoproliferative syndrome caused by homozygous FAS mutations with normal or residual protein expression as well as a novel AR transcription factor 3 deficiency. Finally, we identified several founder effects for specific AR mutations. This did facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families. All together, these findings highlight the specific nature of highly consanguineous populations and confirm the importance of unraveling the molecular basis of genetic diseases in this context. Besides providing a better fundamental knowledge of novel pathways, their study is improving diagnosis strategies and appropriate care.

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Section: Investigations Of Homozygosity Mapping and Age Estimation Ofmentioning

confidence: 51%

Section: Molecular Studies and Mode Of Inheritancementioning

confidence: 99%

Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly Consanguineous Population

et al. 2017

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“…Our patient died at age of 18 months of severe denutrition and gastrointestinal infection. However, MHC-II expression deficiency is quite common in North Africa [9–11]. A majority of affected patients belong to consanguineous families particularly from the Maghreb.…”

Section: Discussionmentioning

confidence: 99%

Hypoxemic Bronchiolitis Related to Major Histocompatibility Class II Deficiency

Hammami

Besbès

Hadded

et al. 2013

Case Reports in Medicine

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Major histocompatibility complex class II expression deficiency is an autosomal recessive primary combined immunodeficiency. The prevalence of this deficiency is the highest in Mediterranean areas, especially North Africa. Early diagnosis is essential due to high mortality in the first 2 years of life. Prognosis is very poor when bone marrow transplantation cannot be performed. We report the case of an infant with major histocompatibility complex class II expression deficiency revealed by hypoxemic bronchiolitis due to Pneumocystis jiroveci.

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“…Patients with primary immunodeficiency disorders (PIDs) have a high susceptibility to microbial infections, particularly to enteric viral infections [22-25]. Reports on HCoSV infection in PID patients are very scarce.…”

Section: Introductionmentioning

confidence: 99%

Iterative Excretion of Human Cosaviruses from Different Genotypes Associated with Combined Immunodeficiency Disorder

et al. 2018

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Background: Human cosaviruses (HCoSVs) are newly discovered enteric viruses in the Picornaviridae family. They have been described in non-polio acute flaccid paralysis, diarrheal patients, and healthy individuals. They remain rarely documented in immunodeficient patients. Objectives: This study reports iterative excretion of HCoSVs in a patient with major histocompatibility complex (MHC) class II combined immunodeficiency, a relatively common primary immunodeficiency in consanguineous settings. Methods: A total of 35 samples were collected from a patient followed for oral polio vaccine strains detection in stool samples during a 57-month period. Detection of HCoSVs in stools was performed by nested RT-PCR in the 5′ noncoding region. The genotype identification and screening for recombinant strains was performed by sequencing in the VP1 and 3D genomic regions followed by phylogenetic analysis. Results: The patient was infected with HCoSVs twice at a 3-year interval. The excreted viruses belonged to 2 different genotypes with 2 probable recombinant viruses. During HCoSV infections, the patient was also excreting Sabin-related polioviruses. Conclusions: This study describes excretion kinetics and genetic characteristics of HCoSVs in a patient with combined immunodeficiency due to MHC class II expression defect. The patient did not have concomitant symptoms related to the HCoSV infection.

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Clinical, Immunological and Genetic Findings of a Large Tunisian Series of Major Histocompatibility Complex Class II Deficiency Patients

Cited by 38 publications

References 24 publications

Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly Consanguineous Population

Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly Consanguineous Population

Hypoxemic Bronchiolitis Related to Major Histocompatibility Class II Deficiency

Iterative Excretion of Human Cosaviruses from Different Genotypes Associated with Combined Immunodeficiency Disorder

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