Link to Pubmed [PMID] – 28692793
BACKGROUND: Sjögren’s syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease suggesting a dose effect on the X chromosome.
METHODS: We examined cohorts of Sjögren’s syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects.
RESULTS: Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjögren’s syndrome, one patient had 45,X/46,XX/47,XXX with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication were found among controls. In another Sjögren’s cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer.
CONCLUSIONS: Very rare X chromosome abnormalities are present among patients with either Sjögren’s or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.