What is inherited immunoglobulin deficiency ??

What is Inherited TBG deficiency ??

In most cases, the cause of inherited TBG deficiency (partial or complete) is a mutation in the coding region of the TBG gene, located on the long arm of chromosome X.  Rarely, other germ line genetic defects lead to a familial absence of or reduction in TBG expression.

Because familial TBG deficiency is X linked, in families with complete TBG deficiency, males have no detectable TBG, while carrier females have half the normal concentration. In families with partial deficiency, males have some measurable TBG concentration, while females tend to have TBG levels that are higher than half the normal concentration. 

The genetic basis of TBG deficiency pertains to point mutations resulting in amino acid substitutions in the mature protein or in truncations caused by stop codons. 

More rarely, TBG defects are caused by aberrant messenger ribonucleic acid (mRNA) processing due to mutations in the acceptor splice site or by exon skipping, as well as a probable defect in TBG-specific transcription factors. ^] Additionally, in the case of a single pedigree, partial TBG deficiency was found to be caused by a mutation in the signal peptide for that protein (ie, in the absence of mutation within the mature peptide). Finally, 2 pedigrees have been described in which, in the deoxyribonucleic acid (DNA) of members of the group who had complete TBG deficiency, no mutations were found in either the signal peptide or in the actual coding regions of the gene. In these 2 pedigrees, the deficiency is believed to have been caused by an overactive silencer located a considerable distance from the TBG gene promoter. ^[] Research has revealed an increasingly complex variety of genetic mechanisms leading to TBG deficiency.

Inherited TBG deficiency also has been described within the context of the genetic syndrome known as congenital disorder of glycosylation type 1 (CDG1), or Jaeken syndrome. The features of this syndrome are psychomotor retardation, cerebellar ataxia, peripheral sensorimotor neuropathy, skeletal abnormalities, lipodystrophy, and retinitis pigmentosa^] CDG1 is caused by mutations in phosphomannomutase 2 and shows autosomal recessive inheritance. ^[ The CDG1 gene locus is located on chromosomal band 16p13 in humans.

In addition to quantitative defects in TBG, qualitative defects resulting in lower T4 affinity or increased degradation due to improper intracellular processing have been described.