Genetic counselling in carriers of reciprocal chromosomal translocations involving short arm of chromosome X

Panasiuk, Barbara; Ušinskiené, Ruta; Kostyk, Ewa; Rybalko, A.; Stasiewicz‐Jarocka, Beata; Krzykwa, B; Pieńkowska-Grela, Barbara; Kučinskas, Vaidutis; Michalova, Kyra; Midro, Alina T.

doi:10.1016/j.anngen.2004.01.001

Cited by 17 publications

(11 citation statements)

References 28 publications

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“…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

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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.

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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

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“…It is likely that a functional trisomy may have additional phenotypic impact in comparison with a functional disomy. Features were commonly seen in cases of Panasiuk et al (2004), Melaragno et al (1998) and Gustashaw et al (1994).…”

Section: Formation Of Neocentric Smcsmentioning

confidence: 99%

“…We have compared the clinical features observed in our case with those commonly seen in the several known cases with a functional disomy of Xp (Gustashaw et al, 1994;Melaragno et al, 1998;Panasiuk et al, 2004) ( Table 1 ). Our case has shared many dysmorphic features with the above cases.…”

Section: Formation Of Neocentric Smcsmentioning

confidence: 99%

“…Meanwhile, it was noted that transcription and 'chromatinboundary activity' were permissible at a neocentromere through selective hypomethylation of pockets of sequences without compromising its overall silent chromatin state and function (Wong et al, 2006). Genotype/phenotype correlation Several cases with 'pure' extra copies of partial Xp containing Xp21.2 ] pter (Gustashaw et al, 1994), Xp22 ] pter (Melaragno et al, 1998) and Xp22.1 ] pter (Panasiuk et al, 2004) have been reported. In these cases, the extra copy of the partial Xp segment was translocated onto the short arm of an acrocentric chromosome, leading to physical separation of the Xp segment from the X inactivation center.…”

Section: Formation Of Neocentric Smcsmentioning

confidence: 99%

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Characterization of a neocentric supernumerary marker chromosome originating from the Xp distal region by FISH, CENP-C staining, and array CGH

Barbouth

Benke

et al. 2007

Cytogenet Genome Res

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A small supernumerary marker chromosome (SMC) was observed in a girl with severe developmental delay. Her dysmorphism included prominent forehead, hypertelorism, down-slanting palpebral fissures, low-set/large ears, and flat nasal bridge with anteverted nares. This case also presented hypotonia, hypermobility of joints, congenital heart defect, umbilical hernia, failure to thrive, and seizures. The SMC originated from the distal region of Xp as identified by FISH with multiple DNA probes. Staining with antibodies to Centromere Protein C (CENP-C) demonstrated a neocentromere, while FISH with an α-satellite DNA probe showed no hybridization to the SMC. A karyotype was described as 47,XX,+neo(X)(pter→p22.31::p22.31→pter), indicating a partial tetrasomy of Xp22.31→pter. This karyotype represents a functional trisomy for Xp22.31→pter and a functional tetrasomy for the pseudoautosomal region given that there is no X-inactivation center in the marker chromosome. The SMC was further characterized by microarray-based comparative genomic hybridization (array CGH) as a duplicated DNA fragment of approximately 13 megabase pairs containing about 100 genes. We have described here a new neocentromere with discussion of its clinical significance.

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“…1,2 The collection of relatively numerous empirical and cytogenetic data of individual RCT carrier pedigrees is necessary to ascertain the risks of malsegregation associated with particular translocations. [5][6][7][8][9] Because the risk of malsegregation is dependent on the size and chromosomal origins of the segments involved and placement of the break points, the accuracy of identifying the break point positions for particular RCT is crucial. High-resolution molecular cytogenetic techniques, like metaphase, interphase and fiber fluorescent in situ hybridization (FISH), sequence-tagged site (STS) marker walking and sequencing of chromosomal regions containing the rearrangement break points and junctions, may be useful for better characterization of specific rearrangements.…”

Section: Introductionmentioning

confidence: 99%

Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2)

et al. 2014

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Cumulative data obtained from two relatively large pedigrees of a unique reciprocal chromosomal translocation (RCT) t(1;11)(p36.22;q12.2) ascertained by three miscarriages (pedigree 1) and the birth of newborn with hydrocephalus and myelomeningocele (pedigree 2) were used to estimate recurrence risks for different pregnancy outcomes. Submicroscopic molecular characterization by fluorescent in situ hybridization (FISH) of RCT break points in representative carriers showed similar rearrangements in both families. Meiotic segregation patterns after sperm analysis by three-color FISH of one male carrier showed all possible outcomes resulting from 2:2 and 3:1 segregations. On the basis of empirical survival data, we suggest that only one form of chromosome imbalance resulting in monosomy 1p36.22→pter with trisomy 11q12.2→qter may be observed in progeny at birth. Segregation analysis of these pedigrees was performed by the indirect method of Stengel-Rutkowski and showed that probability rate for malformed child at birth due to an unbalanced karyotype was 3/48 (6.2±3.5%) after ascertainment correction. The risk for stillbirths/early neonatal deaths was -/48 (<1.1%) and for miscarriages was 17/48 (35.4±6.9%). However, the probability rate for children with a normal phenotype at birth was 28/48 (58.3±7.1%). The results obtained from this study may be used to determine the risks for the various pregnancy outcomes for carriers of t(1;11)(p36.22;q12.2) and can be used for genetic counseling of carriers of this rearrangement.

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Genetic counselling in carriers of reciprocal chromosomal translocations involving short arm of chromosome X

Cited by 17 publications

References 28 publications

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

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

Characterization of a neocentric supernumerary marker chromosome originating from the Xp distal region by FISH, CENP-C staining, and array CGH

Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2)

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