Mapping susceptibility gene locus for IgA deficiency at del(18)(q22.3–q23); report of familial cryptic chromosome t(18q; 10p) translocations

Abstract

This study presents a clinical report of the Finnish chromosome t(18q; 10p) translocation family with an overview of eight other selected immunoglobulin A (IgA)-deficient 18q deletion (18q-) patients from seven published articles. The family members show features common to 18q- syndrome such as mental retardation, multiple facial dysmorphism, foot/hand deformities, abnormal myelination of brain white matter, and a spectrum of immunological/infectious disorders including IgA deficiency (IgAD). Genotype-phenotype correlation study of the unbalanced t(18q-; 10p+) translocation family members and other 18q- syndrome reports led to definition of a potential susceptibility gene locus for IgAD at distal region of 18q22.3-q23 between markers D18S812-18qter. The haplo-insufficiency of the 18q22.3-q23 gene region is suggested to be a cause of the IgAD phenotype in 18q- individuals. This 7 Mb IgAD critical region shows significant association with susceptibility region for celiac disease that is frequently connected to IgAD.

Primary immunodeficiency associated with chromosomal aberration – an ESID survey

“…The other patients in our cohort with chromosome 18q aberrations all but one also showed IgA-deficiency (patients 9, 14, and 20). The two cousins from our study are part of a Finnish family with t (18q;10p), which was published in 2007 [ 20 ]. All members of this family showed IgA-deficiency; IgG-subclasses were not tested in the other family members.…”

Selective IgA Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management

“…The heterogeneous nature of SIgAD recommends that different aetiologies and/or modifier genes may cause the disease . Chromosomal abnormalities and cytogenetic defects have been frequently reported in patients with IgAD including monosomy 4p, trisomy 8, trisomy 10p, translocation of 10q to 4p, 17p11.2 deletions, 18q‐syndrome, trisomy 21, monosomy 22 and 22q11.2 deletion syndrome . Recently, we have reviewed monogenic mutations that are associated with selective IgA deficiency .…”

Immunological Approach of the Challenges of the XXI Century in Celiac Disease

“…A clinical report of the Finnish chromosome t (18q; 10p) translocation family with an overview of eight other selected IgA-deficient 18q deletion (18q-) patients from seven published articles was presented. The haplo-insufficiency of the 18q22.3-q23 gene region was suggested to be a cause of the IgAD phenotype in 18qpeople [33]. The density of TCR gammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD were analyzed.…”