Analysis of genetic variability in Turner syndrome linked to long-term clinical features

Background Women with Turner syndrome (TS) (45,X and related karyotypes) have an increased prevalence of conditions such as diabetes mellitus, obesity, hypothyroidism, autoimmunity, hypertension, congenital cardiovascular anomalies (CCA). Whilst the risk developing these co-morbidities may be partly to haploinsufficiency key genes on X chromosome, other mechanisms involved. Improving our understanding underlying processes is important develop personalized approaches management. Objective We investigated whether: 1) global genetic variability differs in women TS, which might contribute co-morbidities; 2) common variants - background are associated phenotype (a “two-hit” hypothesis); 3) previously reported association autosomal TIMP3 CCA can replicated. Methods Whole exome sequencing was undertaken leukocyte DNA from 134 adult TS compared 46,XX controls (n=23), primary ovarian insufficiency (n=101), 46,XY (n=11). Variability chromosome analyzed for all individuals; relation between long-term phenotypes listed above a subgroup monosomy X; variance CCA. Results Standard filtering identified 6,457,085 126,335 entire cohort, whereas somatic variant pipeline 16,223 477 changes. Overall similar control/comparison groups, were proportionate complement material; when adjusted multiple comparisons, no gene/variants strongly enriched without conditions, although several interest emerged; 22:32857305:C-T found (CCA 13.6%; non-CCA 3.4%, p<0.02). Conclusions do not excess analysis. No obvious X-chromosome driving found, but possible genes/variants emerged. A cardiac