Genetic Aspects of Immunoglobulin A Deficiency

Cunningham‐Rundles, Charlotte

doi:10.1007/978-1-4757-9065-8_4

Cited by 19 publications

(7 citation statements)

References 93 publications

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“…[4] IgA levels lower than 10 mg/dl when other immunoglobulin levels are normal indicates selective IgA deficiency. This rarely accompanying feature has been previously reported both in 18p deletions, and also in 18q deletions [2,5,6] While reports of immunodeficiency with 18p deletion syndrome have mainly focused on selective IgA deficiency, some patients may have low levels of other immunoglubulins also [7]. A patient with monosomy 18p, diagnosed in adulthood, is herein presented with his clinical and molecular findings.…”

Section: Introductionsupporting

confidence: 55%

An Adult Patient with Monosomy 18p, Growth Hormone Deficiency and Selective IgA Deficiency

AkkuA¹,

Çetinkaya²

2016

J Genet Syndr Gene Ther

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Monosomy 18p is a relatively frequent deletion syndrome with an estimated frequency of one in 50,000 liveborns. Most frequent findings consist of mild to moderate growth deficiency, intellectual disability, microcephaly, and facial dysmorphic features including ptosis, epicanthic folds, low nasal bridge, hypertelorism and large protruding ears. Anomalies of other systems may accompany. A 31-year-old male patient with dysmorphic facial features, congenital hypothyroidism, growth hormone deficiency and intellectual disability was diagnosed with monosomy 18p. The patient who also suffered from recurrent aphthous stomatitis and otitis during childhood and selective IgA deficiency was also diagnosed. Monosomy 18p in this patient was further analyzed with SNP microarrays. The 18p deletion caused monosomy of a segment larger than 18 Mb, which consisted many OMIM genes. Deleted genes in this region are known to have a diverse array of functions in various cellular processes. Estimating the possible pathogenic roles of these gene deletions over cellular functions may be difficult for today, however, precise delineation of molecular findings would lead to a better understanding of disease pathogenesis in future.

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Section: Introductionsupporting

confidence: 55%

An Adult Patient with Monosomy 18p, Growth Hormone Deficiency and Selective IgA Deficiency

AkkuA¹,

Çetinkaya²

2016

J Genet Syndr Gene Ther

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“…2 and 3 and the literature ( 10, 24, 25, 41) that simple inspection or even more elaborate analysis of the inheritance of Igd in families cannot provide information about dominant or recessive inheritance. Although this inability to use family inheritance patterns was evident earlier in IgAd and CVID ( 10, 24, 25, 41), our present observations suggest that it is true of all of the Igd determined by [HLA‐B8, SC01, DR3]. The problem is at least partially due to incomplete penetrance of the MHC susceptibility genes.…”

Section: Discussionmentioning

confidence: 99%

“…Family studies fail to reveal a mode of genetic transmission of IgAd or CVID ( 10, 24, 25), mainly because most immediate family members are unaffected. This is at least partially due to incomplete penetrance of the MHC susceptibility genes.…”

mentioning

confidence: 99%

Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA‐B8, SC01, DR3] conserved extended haplotype

et al. 2000

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The extended major histocompatibility complex (MHC) haplotype [HLA-B8, SC01, DR3] is increased in frequency among patients with immunoglobulin (Ig)A deficiency and common variable immunodeficiency. Because the genomic region from HLA-B to HLA-DR/DQ is virtually the same on all instances of the haplotype in the general population, we reasoned that all independent instances of [HLA-B8, SC01, DR3] carry MHC susceptibility genes for these disorders. To define immunoglobulin deficiencies determined by genes on this haplotype and their mode of expression and penetrance, serum immunoglobulin class and IgG subclass concentrations were determined prospectively in homozygotes and heterozygotes of this haplotype and in Caucasian controls. Prevalence of individual immunoglobulin deficiencies in persons with [HLA-B8, SC01, DR3] ranged from 13% to 37%, significantly higher than rates in non-carriers or general controls. We found significantly increased frequencies of IgA and IgG4 deficiency only in homozygotes (13.3% and 30%, respectively) compared with heterozygotes (1.7% and 3.4%) or non-carriers (1.6% each), suggesting recessive expression. In contrast, IgD and IgG3 deficiencies were significantly more common in both homozygotes (36.7% and 30%) and heterozygotes (20.3% and 17.5%) compared with controls (4.9% and 3.4%), suggesting dominant inheritance. These results indicate multiple distinct susceptibility genes, some recessive and others dominant, for deficiency of IgA, IgD, IgG3 or IgG4 (but not for IgE, IgG1, IgG2 or IgM) on [HLA-B8, SC01, DR3]. These observations may also help to explain the observed associations of [HLA-B8, SC01, DR3] with both IgA deficiency and common variable immunodeficiency and the common occurrence of IgG subclass deficiencies in some patients with IgA deficiency.

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“…Modifying genetic factors and genetic associations, which may contribute either to the pathogenesis of the IgAD or other visible complications among patients, were suggested by studies that evaluated the underlying genetic defects of patients. In reported familial cases, inheritance of IgA deficiency is either autosomal dominant or autosomal recessive based on the pedigree analysis, but sporadic cases show no genetic associations [16, 17]. To date, identified defects of both MHC and non-MHC genes are summarized in the following sections.…”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

“…From a genetic point of view, 3 chromosomes including 18, 14, and 6 have been significantly associated with IgA deficiency according to the genome-wide association studies [16]. In this sense, the mode of inheritance is not fully understood; certain human leukocyte antigens (HLA) haplotypes and non-HLA genes have been associated with IgA deficiency.…”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

Bagheri¹,

Sanaei²,

Yazdani³

et al. 2019

Int Arch Allergy Immunol

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Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.

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Genetic Aspects of Immunoglobulin A Deficiency

Cited by 19 publications

References 93 publications

An Adult Patient with Monosomy 18p, Growth Hormone Deficiency and Selective IgA Deficiency

An Adult Patient with Monosomy 18p, Growth Hormone Deficiency and Selective IgA Deficiency

Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA‐B8, SC01, DR3] conserved extended haplotype

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

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