Combined trisomy 9 and Ullrich-Turner syndrome in a girl with a 46,X,der(9)t(X;9)(q12;q32) karyotype

Can�n, Sonia; Mutchinick, Osvaldo M.; Shaffer, Lisa G.; Fern�ndez, Camilo

doi:10.1002/(sici)1096-8628(19981116)80:3<199::aid-ajmg3>3.0.co;2-p

Cited by 8 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, there are many cases in which the attenuated phenotype of individuals trisomic for a segment of autosome, translocated onto an inactive X, appears to be correlated well with the spreading of late replication into it (Canun et al 1998;Disteche et al 1984;Keitges and Palmer 1986;Mohandas et al 1982;Williams and Dear 1987). Such cases imply that the inactivated region of autosome can be defined by the extent of spread of late replication.…”

Section: Discussionmentioning

confidence: 99%

Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation

2001

View full text Add to dashboard Cite

We have analysed the spread of X inactivation in an individual with an unbalanced 46,X,der(X)t(X;10)(q26.3;q23.3) karyotype. Despite being trisomic for the region 10q23.3-qter, both the proband and her aunt with the same karyotype presented only with secondary amenorrhoea and lacked any features normally associated with trisomy of distal 10q. Cytogenetic and molecular studies showed that the derivative X;10 chromosome was exclusively inactive. Transcribed polymorphisms were identified in five genes contained within the translocated region of chromosome 10 and were used to perform allele-specific transcription studies. We showed that four of the genes studied are inactive on the derivative chromosome, directly demonstrating the spread of X inactivation over some 30 Mb of autosomal DNA. However, the most distal gene examined remained active, indicating that this spreading was incomplete. In contrast to the gene expression data, replication timing studies showed no spreading of late replication into the translocated portion of 10q. We conclude that silencing of autosomal genes by X inactivation can occur without a delay in the replication timing of the surrounding chromatin. Our findings support the hypothesis that autosomal chromatin lacks certain features present on the X chromosome that are required for the effective spread and/or maintenance of X inactivation.

show abstract

Section: Discussionmentioning

confidence: 99%

Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation

2001

View full text Add to dashboard Cite

show abstract

“…Spreading of XIST RNA into the translocated autosomal segment appears to be a plausible mechanism for autosomal gene silencing. However, cytogenetic and molecular studies show incomplete or discontinuous XIST RNA spreading and either limited or even absence of a correlation between late replication of autosomal material and gene silencing in cells from patients with an attenuated phenotype [Keitges and Palmer, 1986; Schanz and Steinbach, 1989; Bettio et al, 1994; Kulharya et al, 1995; Garcia‐Heras et al, 1997; Canún et al, 1998; Bacino et al, 1999; Blennow and Sahlén, 1999; Duthie et al, 1999; Keohane et al, 1999; Abuelo et al, 2000; Sharp et al, 2001, 2002; Waters et al, 2001; Hall et al, 2002; Gläser et al, 2004; Panasiuk et al, 2004; Yatsenko et al, 2004]. It has been suggested that autosomal chromatin lacks some features necessary for spreading and maintenance of X inactivation [Keohane et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation

Stankiewicz

Kuechler

Eller³

et al. 2006

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Few cases of de novo unbalanced X;autosome translocations associated with a normal or mild dysmorphic phenotype have been described. We report a 3-year-old dizygotic female twin with prenatally ascertained increased nuchal translucency. Prenatal chromosome studies revealed nearly complete trisomy 15 due to a de novo unbalanced translocation t(X;15)(q22;q11.2) confirmed postnatally. A mild phenotype was observed with normal birth measurements, minor facial dysmorphic features (hypertelorism, short broad nose, and a relatively long philtrum), and moderate developmental delay at the age of 3 years in comparison to her male fraternal twin. Replication timing utilizing BrdU and acridine-orange staining showed that the der(X) chromosome was late-replicating with variable spreading of inactivation into the translocated 15q segment. The der(X) was determined to be of paternal origin by analyses of polymorphic markers and CGG-repeat at FMR1. Methylation analysis at the SNRPN locus and analysis of microsatellites on 15q revealed paternal isodisomy with double dosage for all markers and the unmethylated SNRPN gene. The Xq breakpoint was mapped within two overlapping BAC clones RP11-575K24 and RP13-483F6 at Xq22.3 and the 15q breakpoint to 15q11.2, within overlapping clones RP11-509A17 and RP11-382A4 that are all significantly enriched for LINE-1 elements (36.6%, 43.0%, 26.6%, 22.0%, respectively). We speculate that the attenuated phenotype may be due to inactivation spreading into 15q, potentially facilitated by the enrichment of LINE-1 elements at the breakpoints. In silico analysis of breakpoint regions revealed the presence of highly identical low-copy repeats (LCRs) at both breakpoints, potentially involved in generating the translocation.

show abstract

“…In any event, these active genes apparently have not adversely affected their patient's phenotype. Other recent reports in which partial autosomal trisomies resulting from X‐chromosome translocations have resulted in mild phenotypes include partial trisomy 3p [Bettio et al, 1994; Kulharya et al, 1995], partial trisomy 9 [Canún et al, 1998], partial trisomy 16q (Bacino et al, [1999], and partial trisomy 13q [Blennow and Sahlén, 1999]. In the latter case, the researchers thought their patient had been “rescued” from the effects of trisomy 13q by the effects of skewed inactivation.…”

Section: Discussionmentioning

confidence: 98%

Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting

2000

View full text Add to dashboard Cite

We describe the case of a 13-year-old girl with an apparently de novo unbalanced translocation resulting in the presence of additional chromosomal material on the short arm of one X chromosome, which was detected by conventional G-banding studies. Fluorescence in situ hybridization (FISH) using the Chromoprobe Multiprobe-M protocol confirmed that the additional chromosomal material originated from chromosome 5. The karyotype of this patient is now established to be 46,X,der(X) t(X;5)(p22.3;q33), with a deletion of Xp22.3-pter and partial trisomy of 5q33-qter. The distal 5q trisomy genotype has been associated with clinical signs that include growth and mental retardation, eczema, craniofacial anomalies, and malformations of heart, lungs, abdomen, limbs, and genitalia. Our patient also has short stature, a prominent nasal bridge, a flat philtrum, a thin upper lip, dental caries, and limb and cardiac malformations, but she appears to be mildly affected compared with previously reported cases. This is the first case of distal 5q trisomy arising from a translocation with the X chromosome. Replication studies on this patient show that the derivative t(X;5) chromosome is late replicating in almost all cells examined, which indicates that this chromosome is preferentially inactivated. However, the translocated segment of chromosome 5 appears to be early replicating, which implies that the trisomic 5q segment is transcriptionally active. We cannot determine from these studies whether all or only some genes in this segment are expressed, but this patient's relatively mild clinical signs suggest that the critical region(s) that contribute to the distal 5q trisomy phenotype are at least partly suppressed. A review of other patients with X-chromosome translocations indicates that many but not all of them also have attenuated phenotypes. The mechanism of inactivation of autosomal material attached to the X chromosome is complex, with varying effects on the phenotype of the patients that depend on the nature of the autosomal chromatin. Replication studies are of limited utility in predicting expression of autosomal genes involved in X-chromosome translocations.

show abstract

Combined trisomy 9 and Ullrich-Turner syndrome in a girl with a 46,X,der(9)t(X;9)(q12;q32) karyotype

Cited by 8 publications

References 11 publications

Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation

Absence of correlation between late-replication and spreading of X inactivation in an X;autosome translocation

Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation

Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting

Contact Info

Product

Resources

About