TS is a chromosomal disorder in females. Classic TS patients have the karyotype 45,X. Some other TS patients can present with mosaicism or have a structurally rearranged X karyotype . Patients who carry a structurally abnormal X chromosome are a unique group, and they have provided opportunities to evaluate genotype/phenotype correlations in relation to X chromosome content and inactivation. Mosaicism karyotypes with structurally abnormal ring chromosomes are even rarer, accounting for only 5% of TS patients .
We here describe a 10 year old girl who had short stature and ovarian dysplasia. She was found to have a de novo mosaic 45,X/46,X, + r (p22.32q21.1) by cytogenetic analysis. The observed deletion of p22.32p22.33 [4.8 Mb] and Xq21.1-Xq28 was approximately 75 Mb in size, and harbored 605 genes. We found several similar cases associated with our case where a ring chromosome has been described previously. For example, the cases Xpter-Xp22.12 [21 MB] and Xq21.33-Xq28 [62 Mb] had more severe symptoms than our case, and these case’s deletion fragment contained 789 genes compared to our case, which only contained 605 . This difference in symptom severity could be explained by the amount of X deletion and the number of genes contained in the deleted region. It was also possible that the difference in severity between the cases was due to differences in the degree of mosaicism for two cell lines 45, X and 46, Xr (X) (70:30 in ou case compared to 50:50 in the more sever case). However, it is difficult to ascertain the impact of mosaicism on clinical phenotype as level of mosaicism has been reported to go down with age due to the unstable nature of r (X) chromosomes.
Furthermore, we compared Xp deletions and clinical presentations in our case to those of previously reported cases that showed no evidence of ovarian dysgenesis with an Xp terminal deletion, Here, we report a rare case of TS with an X ring mosaicism karyotype of 45,X and 46,X, r(X)(p22.32q21.1). This case had an atypical phenotype. For example, her intellectual development did not lag behind her peers, and the patient’s breast development was Tanner stage 2. Other symptoms are described in Table 1. A case similar to ours (Xpter-Xp22.12 and Xpter-Xp22.31, respectively) had been reported in (Xp22.33-Xp22.12) without any sign of ovarian dysgenesis [7,8,9]. Therefore, we considered ovarian dysgenesis in our case might have been due to Xq deletion rather than Xp deletion.
Previous studies have found that ring X chromosomes, which are active, as defined by deficient XIST transcription, are present in females who have mental retardation and multiple congenital abnormalities [10, 11]. Small ring (X) chromosomes lacking the XIST gene have been associated with a severe phenotype that includes mental retardation, facial dysmorphism, and congenital abnormalities [10, 12]. It has been hypothesized that the loss of XIST results in functional disomy for the sequences contained in the ring. However, in our case, XIST was intact with the ring chromosome negating the role of XIST inactivation in the clinical phenotype of patients. Therefore, we believe that the results of ring X formation was most likely inactivation in our case.
Moreover, the loss of different genetic material leads to different clinical phenotypes in Turner syndrome, and the chromosomal karyotype and clinical phenotype are dependent. Short stature is the most common characteristic, and is caused by the perturbations of the SHOX gene on Xp22.3 [7, 8, 13]. The key region determining the development of female gonads is in Xq21-Xq27, and the disruption of these regions will lead to female ovarian dysplasia [14, 15]. Our case was consistent with the phenotype reported in previous studies. The clinical phenotype of our case was less severe than that of a classic 45X karyotype, which may be related to mosaicism of the ring X chromosome, but this is still as uncertain.
In summary, we describe the phenotype in terms of clinical symptoms, ultrasound diagnosis, and cytogenetics, of a girl with a rare genotype and TS. We discussed the similarities and differences between our case and other previously reported cases with similar genotypes. We used a combination of techniques and analysis of information from public gene databases (Decipher/Clingen/UCSC/Pubmed) to provide additional evidence to clarify the genotype-phenotypic associations of TS, which can facilitate further genetic counseling and enrich database information on TS.