45，X／46，X，ter rea（X；X）一例

患者 社会性别女，24岁，未婚。因原发性闭经就诊。智力无异常。父母非近亲婚配。家族中否认遗传病和其他特殊病史。查体：身高173cm，体重62kg。无特殊面容，发际不低，无颈蹼，指间距174cm，无肘外翻。双侧乳房发育欠佳，乳间距宽。外阴呈幼稚型、阴毛稀少。B超示：始基子宫，双侧卵巢未探及，有阴道。     

45,X/46,X,idic(X)两例

例1 女,16岁,无月经来潮,身材矮小,身高138cm,表情呆滞,反应迟钝.查体:头发浓密,发际低,轻度蹼颈,肘外翻明显,女性第二性征无发育.外生殖器呈女性特征,阴毛稀疏,大小阴唇幼稚型.激素水平测定:促卵泡激素和黄体激素水平高于正常,与绝经期女性值相近,雌二醇(E2)测定值很低.B超提示:始基子宫.细胞遗传学检查:常规外周血淋巴细胞染色体培养、核型分析.     

46,X,der(X)一例

患者 女孩表型,7岁,骨龄5岁,身材矮小,身高106.5cm.出生史和家族史无异常.面容正常,智力正常.     

Growth disadvantage of 45,X and 46,X,del (X) (p11) fibroblasts

We have previously shown that cell generation time (CGT) is prolonged in 45,X and certain X-deletion fibroblast lines (Simpson & Le Beau 1981). A consequence of that finding should be that cells with 45,X or an X-structural abnormality are at a competitive disadvantage when cocultivated with 46,XX cells. To test this hypothesis we prepared 15 minutes of cells from combinations of 9 different cell lines: four 45,X; one 46,Xdel(X)(p11); and four 46,XX. Each culture was monitored cytogenetically at frequent passage intervals for the percentage of the two cell lines. Significant differences were found between normal and abnormal lines in culture predominance, in the order predicted by our hypothesis (p less than 0.01). The specific mechanism by which absence of an X chromosome confers growth disadvantage is unknown, but is consistent with prolongation of CGT. Prolongation of CGT could also be responsible for the embryonic lethality, intrauterine growth retardation, short stature, and somatic anomalies commonly observed in individuals with absent or aberrant X chromosomes.     

Novel karyotype in the Ullrich-Turner syndrome—45,X/46,X,r(X)/46,X,dic(X)—investigated with fluorescence in situ hybridization

A 10-year-old girl with Ullrich-Turner syndrome was found to have the novel karyotype 45,X/46,X,r(X)(p11q11)/46,X,dic(X)(p11). Fluorescence in situ hybridization (FISH) with the α satellite X centromere probe established the origin of the small ring chromosome. Scanning a large number of cells by interphase FISH showed that the dicentric (X) was the least prevalent cell line. The common breakpoint of Xp11 suggests a sequence of errors as the mechanism whereby these 3 distinct cell lines have arisen. © 1994 Wiley-Liss, Inc.     

A woman with an apparent non-mosaic 45,X delivered a 46,X,der(X) liveborn female

A liveborn female with a phenotype suggestive of Down syndrome is reported. Cytogenetic lymphocyte analysis showed a 46,X der(X) karyo-type. Fluorescence in situ hybridization (FISH) with a biotinylated probe specific for chromosome 21 showed no signal on the der(X). This marker was homogeneously painted using a specific probe for X chromosome. In addition, FISH analysis detected telomeres on the rearranged X. Therefore, the proband's karyotype was revaluated as 46,X,del(X) (pter p22.2::p11.3 qter). Cytogenetic analysis of 150 lymphocytes in the mother disclosed a homogeneous 45,X karyotype. FISH analysis of interphase nuclei using the X chromosome painting probe showed two domains of different sizes in 0.8% of cells. This led us to study further metaphases in the mother. In one out of 450 metaphases scored, after FISH with the X chromosome painting probe, the del(X) was observed, confirming that the rearranged X chromosome found in the newborn had segregated from a 45,X/46,X,del(X) mother.     

Discordant phenotypes and 45,X/46,X,idic(Y).

Mosaicism introduces wide variability into the clinical expression of numerical and unbalanced structural chromosomal abnormalities. The phenotypic range of variability of 45,X/46,XY mosaicism extends from Turner syndrome to mixed gonadal dysgenesis to normal males. The specific phenotype is primarily dependent on the chromosomal constitution of the developing gonad. Similar phenotypic variability is observed with mosaicism for 45,X and a second cell line with an abnormal sex chromosome. This report describes a patient with Turner syndrome and a patient with mixed gonadal dysgenesis who have identical karyotypes, namely 45,X/46,X,idic(Y)(p11.2). While mosaicism alone might have accounted for the phenotypic differences, by PCR analysis the Turner syndrome patient was SRY and ZFY negative and the mixed gonadal dysgenesis patient was SRY and ZFY positive.     

45，X／46，Xr（X）（p22．2∷q13）一例

患儿女，10岁。第1胎，足月顺产。因生长发育迟缓，来我室就诊。患儿出生时一般情况良好，生后身高增长缓慢，就诊时身高110cm，肘外翻，外眼角上斜，有条索状性腺，表现为Turner综合征体征，但无蹼颈。双亲表型正常，非近亲婚配，患儿出生时父龄27岁，母龄25岁，其母孕期无感冒、发热、也无化学药物及放射线物质接触史，家族中无类似病史。     

X chromosome inactivation patterns in 45,X/46,XX mosaics

To investigate X chromosome inactivation (XCI) patterns in 45,X/46,XX mosaics, genomic DNA was extracted from peripheral blood samples of 15 female subjects who showed different proportions of 45,X cell clones. XCI patterns were analyzed using two assays. The first assay was the BstXI restriction endonuclease detection of an X-linked phosphoglycerate kinase (PGK) gene polymorphism following digestion of the DNA with methylation-sensitive HpaII, or with methylation-insensitive AfaI as a control. The second assay was the detection of a CAG triplet repeat polymorphism in the X-linked androgen receptor (AR) gene after sodium bisulfite treatment. Of the 15 subjects, 11 were informative due to heterozygosity for at least one of the polymorphisms (6 were heterozygous for the PGK polymorphism and 9 were heterozygous for the AR polymorphism). Four of the 11 informative subjects (36%) showed extremely skewed XCI for at least one of the polymorphisms, which was a much higher incidence than previously reported for normal females. Moreover, 3 of these 4 women had proportions of 45,X cell clones greater than 20%. Although our results may be due to several possible cytogenetic or molecular mechanisms, the most likely explanation is that cases of 45,X/46,XX that contain relatively high levels of 45,X cell clones probably arose due to structural aberrations of the X chromosome undetectable by conventional karyotyping. Received: November 6, 2000 / Accepted: December 18, 2000     

45,X/46,X, + r(X) can have a distinct phenotype different from Ullrich-Turner syndrome

We present a patient with 45,X/46,X, + r(X) mosaicism and lack of inactivation of either the normal or the ring X in the 46,X, + r(X) cells. The patient has mental retardation, syndactyly, minor facial anomalies, and a congenital heart defect. Although most patients with 45,X/46,X, + r(X) have the Ullrich-Turner syndrome, 2 previously described patients with this karyotype also had a distinct phenotype consisting of severe mental retardation, syndactyly, and abnormal face. The unusually severe phenotype in these patients was thought to be due to lack of X-inactivation of the ring X chromosome. The findings in our patient support this hypothesis.     

Gonadal dysgenesis with 45,X/46,X,dic(Yp) mosaicism

A female patient with a gonodal mucinous cystadenoma on the right side and a gonado-blastoma on the left was found to be a 45,X/46,X,dic (Yp) mosaic, This brings the total number of cases with dicentric Y chromosome reported to date to 23.
Together with the available evidence, the information derived from this case supports the hypothesis that the gene on the long arm of the Y chromosome is responsible for the initiation of testicular differentiation, whereas that on the short arm is responsible for the maturation of the testes.     

45X/46X,r(X) with syndactyly and severe mental retardation

Two white females, age 2 1/2 and 33 years, respectively, were investigated because of severe mental retardation associated with neurologic abnormalities, coarse face, and soft tissue syndactyly involving upper and lower limbs. Each had cytogenetic findings of a mosaic variant of Ullrich-Turner syndrome with X ring chromosome in peripheral lymphocyte and skin fibroblasts. Early X replication occurred in one-third of the X ring chromosomes; there was no evidence for X-autosome translocation involving either X and an autosomal duplication; results of studies for fragility of the X chromosomes were unremarkable. In situ hybridization with an X centromere probe was positive for the ring. To our knowledge, the unusual constellation of cytogenetic, physical, and mental findings seen in these 2 individuals has not been reported previously.     

De novo isodicentric X chromosome: 46,X,idic(X)(q24), and summary of literature

We describe a 12-year-old patient, the second live born prenatally ascertained patient in the literature, with a de novo isodicentric X chromosome, karyotype 46,X,idic(X)(q24), with normal growth and development and lack of dysmorphic features. Molecular and cytogenetic studies were performed to further characterize the isodicentric chromosome X behavior. Literature on isodicentric X chromosomes with various breakpoints on Xq is reviewed and summarized.     

45,X/46,X,+r(X) can have a distinct phenotype different from Ullrich-Turner syndrome.

We present a patient with 45,X/46,X,+r(X) mosaicism and lack of inactivation of either the normal or the ring X in the 46,X,+r(X) cells. The patient has mental retardation, syndactyly, minor facial anomalies, and a congenital heart defect. Although most patients with 45,X/46,X,+r(X) have the Ullrich-Turner syndrome, 2 previously described patients with this karyotype also had a distinct phenotype consisting of severe mental retardation, syndactyly, and abnormal face. The unusually severe phenotype in these patients was thought to be due to lack of X-inactivation of the ring X chromosome. The findings in our patient support this hypothesis.     

46, X,X-X terminal rearrangement /45, X mosaicism in a child with short stature

A phenotypically female child, investigated because of short stature, had abnormally large, often bipartite Barr bodies and a mosaicism of 45,X cells and cells with 46 chromosomes which included an exceptionally large metacentric chromosome (Xp +). G- and C-banding established that the chromosome was derived from two substantially entire X chromosomes joined short arm-to-short arm, and was likely to be an isodicentric X with functional in-activation of one centromere.     

Male with 45, X karyotype

A 5-month-old male child with the clinical stigmata of Turner syndrome, bilateral testes and a non-mosaic 45, X karyotype in blood and skin tissue is presented. This is the second case reported in the literature of an "XO-male" with normal external genitalia.