Linkage analysis in a large kindred with autosomal dominant transmission of polyglandular autoimmune disease type II (Schmidt syndrome)

Abstract

Schmidt syndrome (PGA syndrome type II) is a rare condition characterized by polyglandular failure. It is an autosomal dominant trait with variable expressivity that was inherited over four generations in an Indiana kindred. Association of HLA-B8 has been reported with Schmidt syndrome. Our proband is a 12-year-old boy with Addison disease, insulin dependent diabetes mellitus (IDDM), and vitiligo. Two of his eight sibs had either IDDM (sister) or vitiligo and hyperthyroidism (brother). His mother had hypothyroidism. Seven members of earlier generations apparently were also affected. We obtained peripheral blood for HLA and genetic analysis from 21 relatives in a family with 8 Schmidt syndrome individuals in three generations. HLA studies on 15 affected and unaffected relatives showed only 2 of 7 persons with B8-containing haplotypes. Therefore, no association exists between the B8-containing haplotype and the syndrome.We identified informative marker loci. No evidence for linkage of the Schmidt locus to any of the 14 markers was found and close linkage to esterase D and adenylate kinase and possibly properdin factor B was excluded.

Inherited Susceptibility to Autoimmune Addison's Disease Is Linked to Juman Leukocyte Antigens-DR3 and/or DR4, except when Associated with Type I Autoimmune Poluglandular Syndrome*

“…These findings are strongly reminiscent of the known HLA association with IDD as shown in the comparative data in Tables 1 and 2. Whereas there have been recent studied to suggest that familial Addison's disease with type II APS may be related to inheritance of HLA haplotypes (20)(21)(22), especially those containing B8 alleles (6,(13)(14)(15)(21)(22), there are no reports to our knowledge of HLA-DR frequencies in a series of such patients. In this study, there was an increased frequency of B8 as part of the B8-DR3 haplotype among the patients, but not of other B antigens.…”

Vitiligo: A comprehensive overview

“…96 Like APECED, it presents with polyglandular failure (Addison disease, hypothyroidism, and type I diabetes mellitus), and occasionally vitiligo and/or hypogonadism. 97 Vogt-Koyanagi-Harada disease is a rare systemic T-cell mediated disorder characterized by uveitis, aseptic meningitis, dysacusis, alopecia, poliosis, tinnitus, and vitiligo (8-100%). [98][99][100][101][102][103][104] Kabuki syndrome is a rare multiple malformation disorder that is characterized by developmental delay, distinct facial anomalies, congenital heart defects, limb and skeletal anomalies, and short 110 Vitiligo lesions typically appear unremarkable with only scant cellular infiltrates and few or no melanocytes.…”

Modern vitiligo genetics sheds new light on an ancient disease

“…The first vitiligo genetic linkage studies were of candidate genes. A linkage study of the HLA region in a large family with polyglandular autoimmune disease type II (Schmidt syndrome), including with vitiligo, was negative . Tripathi et al .…”