Gonadal dysgenesis in Turner syndrome with Y-chromosome mosaicism:Two case reports

BACKGROUND Turner syndrome(TS)has a variety of different karyotypes,with a wide range of phenotypic features,but the specific karyotype may not always predict the phenotype.TS with Y chromosome mosaicism may have mixed gonadal dysgenesis,and the mosaicism is related to the potential for gonadoblastoma.CASE SUMMARY In this case report,we report two cases of TS with different karyotypes and gonadal dysgenesis.Patient 1 had obvious virilization,and was positive for the SRY gene,but her karyotype in peripheral blood lymphocytes was 45X.Patient 2 had a mosaic karyotype,45X/46X,dic(Y:Y)(p11.3:p11.2),and the proportion of Y-bearing cells was 50%in peripheral blood lymphocytes,but the patient had normal female external genitalia and streaky gonads,with no genital virilism.Different tissues in the same TS individual may exhibit different ratios of mosaicism.The gonadal determination and differentiation of mosaic TS are primarily dependent on the predominant cell line in the gonads.CONCLUSION In TS patients with virilization,it is necessary to test at least two to three tissues to search for cryptic Y material.

Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis

Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal hematopoiesis.This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score(PRS)on cirrhosis risk prediction.Methods:mCA call sets of individuals with European ancestry were obtained from the UK Biobank.The PRS was constructed based on 12 susceptible single-nucleotide poly-morphisms for cirrhosis.Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk.Results:Among 448,645 individuals with a median follow-up of 12.5 years,we identified 2,681 cas-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated cirrhosis.Compared to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%vs.cell fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.