Alopecia Areata & Down Syndrome Abstracts
Clin Exp Dermatol 27 (5): 405-9 (2002 Jul)
Epidemiology and genetics of alopecia areata
McDonagh AJ, Tazi-Ahnini R
Department of Dermatology and Division of Genomic Medicine, Royal Hallamshire Hospital, University of Sheffield, UK
The frequency of alopecia areata and observed patterns of heritability are in keeping with a polygenic inheritance model but the genetics of alopecia areata is still poorly understood. The role of environmental factors in triggering disease initiation or exacerbation remains almost entirely speculative. Using the candidate gene approach, three susceptibility/severity factors have been identified. HLA alleles were the first to show a strong association with alopecia areata and some DQB and DR alleles have been demonstrated to confer a high risk for disease by both case-control and family-based studies. Interleukin (IL)-1 cluster genes, mainly the IL-1 receptor antagonist, show a strong association with disease severity in alopecia areata and a number of other autoimmune and inflammatory diseases. Finally, the association of alopecia areata with Down's syndrome, the high frequency of alopecia areata in autoimmune polyglandular syndrome type I due to mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3 and the finding of association with MX1, another gene in the Down's syndrome region of chromosome 21 indicate this area of the genome as a promising target for future-family based investigations. The role of individual genes of the MHC, IL-1 cluster or chromosome 21q22.3 is difficult to establish and further genetic and functional investigations are needed to confirm their involvement in the pathogenesis of alopecia areata.
Hum Genet 106 (6): 639-45 (2000 Jun)
Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region
Tazi-Ahnini R et al.
Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, UK
Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy hair loss with T-cell infiltration of hair follicles. AA occurs in approximately 0.1% of the general population, but this is increased to 9% in Down syndrome (DS). DS is associated with an additional copy of chromosome 21, and the DS region may potentially include genes involved in the pathogenesis of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). We have previously shown that MxA protein is strongly expressed in lesional anagen hair bulbs from patients with AA but not in normal follicles. We therefore studied the possible involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1 region which could be screened by PCR-based methods, we defined the human MX1 exon/intron organisation and screened the exons and the introns by conformation-sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons extending over 33 kb. The size and sequence of the region from exon 6 to exon 16 are highly conserved between human and mouse. Screening of 4747 bp within the MX1 gene revealed four single nucleotide polymorphisms in intron 6. These polymorphisms are concentrated within 147 bp and show strong linkage disequilibrium. In a case-control association study for the MX1 (+9959) polymorphism in 165 AA patients and 510 controls we found a significant association of this marker with AA. The risk of disease was greater for patchy AA (mild disease) and with early age at onset, providing new evidence of genetic heterogeneity in AA. Our demonstration of genetic association between the MX1 gene and disease supports the hypothesis that this is a new candidate gene in AA.
Ann Dermatol Venereol 105 (6-7): 587-90 (1978 Jun-Jul)
Alopecia areata and trisomy 21. About 2 cases
Doutre MS; Ortonne JP; Floret D; Thivolet J
Two cases of alopecia areata coexisting with trisomy 21 are reported. In the first case, the two diseases were associated with Hashimoto's thyroiditis and in the second, with vitiligo. Pathogenic implications are discussed.
Arch Dermatol 112 (10): 1397-9 (1976 Oct)
Alopecia areata and Down syndrome
Carter DM; Jegasothy BV
The skin of 214 institutionalized patients with the Down syndrome was carefully examined. There were 19 cases of alopecia areata and four cases of vitiligo. Since persons with the Down syndrome are predisposed to immunological deficiency in thymus-dependent (T-cell) function, findings from the skin examinations suggest that immunologic factors might contribute to the increased incidence of vitiligo and alopecia areata seen in the Down syndrome. Syringoma was also common and affected female patients twice as frequently as male patients.
Br Med J 1 (5951): 191-2 (1975 Jan 25)
Alopecia areata, autoimmunity, and Down's syndrome
Du Vivier A; Munro DD
Alopecia areata occurs more often in Down's syndrome than would be expected by chance, sixty cases being found among 1000 patients with this syndrome compared with one case among 1000 subnormal controls. Because alopecia areata is associated with some organ-specific autoimmune disease and thyroid antibodies are often found in Down's syndrome sera from affected patients were examined for the presence of fluorescent autoantibodies. Antibodies against thyroid components tended to be present in female mongols with alopecia areata in comparison with females in a normal population but not in male mongols. Futhermore, eight out of 23 female mongols (35%) with alopecia areata had antibodies against thyroid components compared with two out of 23 female mongols (9%) without alopecia areata.