Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

Sawyer, Jeffrey R.; Swanson, Charles M.; Lukacs, Janet L.; Hassed, Susan J.; Curtis, Mary A.; North, Paula E.; Kozlowski, Karen J.; Pihoker, Catherine

doi:10.1002/(sici)1096-8628(19970414)69:4<383::aid-ajmg9>3.0.co;2-m

Cited by 11 publications

(18 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in comparison with euploid cells, chromosomal instability appears to be more pronounced in TS patients. 22–24 Mosaicism differences between karyotypes and arrays may also be accentuated due to sampling bias, especially if fewer than 50 cells are counted. SNP array analysis of whole blood eliminates the potential for selective pressure due to cell culture and may therefore provide a more accurate representation of mosaicism in peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome

Prakash

Guo

Maslen

et al. 2014

Genetics in Medicine

View full text Add to dashboard Cite

Background Turner syndrome (TS) is a developmental disorder caused by partial or complete monosomy for the X chromosome in 1:2500 females. We hypothesized that single nucleotide polymorphism (SNP) array genotyping can provide superior resolution in comparison to metaphase karyotype analysis to facilitate genotype-phenotype correlations. Methods We genotyped 187 TS patients with 733,000 SNP marker arrays. All cases met diagnostic criteria for TS based on karyotypes (60%) or characteristic physical features. SNP array results confirmed the diagnosis of TS in 100% of cases. Results We identified a single X chromosome (45,X) in 113 cases. In 58 additional cases (31%), other mosaic cell lines were present including isochromosomes (16%), rings (5%) and Xp deletions (8%). The remaining cases were mosaic for monosomy X and normal male or female cell lines. Array-based models of X chromosome structure were compatible with karyotypes in 104 of 116 comparable cases (90%). We found that SNP array data did not detect X;autosome translocations (3 cases), but did identify 2 derivative Y chromosomes and 13 large copy number variants that were not detected by karyotyping. Conclusions Our data is the first systematic comparison between the two methods and supports the utility of SNP array genotyping to address clinical and research questions in TS.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome

Prakash

Guo

Maslen

et al. 2014

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…TAs have been mostly reported in various leukemias and solid tumors (renal tumor, squamous cell carcinoma, cardiac myxoma, giant cell tumor of bone) and exceptionally in constitutional cells. To our knowledge, only seven patients from five different families carrying a constitutional TAs with TTAGGG telomeric sequences at the junction of the TAs have been previously published [Sawyer et al, ; Engelen et al, ; Zneimer et al, ; Huang et al, ; Josifova et al, ] (Table ). We did not include the rare cases for which the presence of telomeric sequences at the junction of the TA was not proven experimentally.…”

Section: Discussionmentioning

confidence: 99%

“…We have no data regarding the females since all of them were very young (less than 11 years). Our female patient and a second one had infertility because of gonadal dysgenesis [Sawyer et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, constitutional TAs are rare events. To our knowledge, five different constitutional TAs have been reported to date [Sawyer et al, ; Engelen et al, ; Zneimer et al, ; Huang et al, ; Josifova et al, ], among them two involved the Y chromosome [Sawyer et al, ; Huang et al, ]. We report on a 6‐year‐old girl for whom a monosomy X was diagnosed during pregnancy.…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Constitutional telomeric association (Y;7) in a patient with a female phenotype

Bénéteau

Baron

David

et al. 2013

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Telomeric associations (TAs) are fusions between two telomeres of two different chromosomes without visible loss of chromosomal material. Constitutional telomeric associations are rare chromosomal anomalies. We report on the cytogenetic and molecular analyses of a TA involving chromosomes Y and 7 in a child with a female phenotype. Prenatal cytogenetic analysis showed a 45,X chromosome complement in all cells. No fetal abnormality was identified at ultrasound examinations and the pregnancy went to term. During childhood, the proband had gonadal dysgenesis but no other phenotypic manifestations of Turner syndrome. Molecular genetic analyses showed the presence of genomic DNA of the SRY gene without any mutation. Karyotyping and fluorescent in situ hybridization (FISH) analyses on blood showed two cell lines: one cell line with a TA involving chromosomes Y and 7 [46,X,tas(Y;7)(p11.32;q36.3)] and a second cell line with a 45,X pattern. A human pantelomeric repeat TTAGGG probe hybridized to the junction of the TA within the derivative chromosome. FISH and array comparative genomic hybridization (aCGH) analyses demonstrated that tas(Y;7) occurred without detectable loss of any sequence at the derivative chromosome. SNP array analysis excluded an uniparental isodisomy of chromosome 7. Knowing more about TAs will help geneticists to deliver accurate genetic counseling.

show abstract

“…Two additional cell lines were seen in the left gonad: 46,X,tas(Y; 21)(q12; p13),−22 and 46,X,tas(Y; 21)(q12; p13),+tas(Y; 14)(q12; p13),−22. The Yqter was in telomere association with chromosome 21 short arm in the skin, peritoneum, fascia, and right gonad and in tas with chromosomes 14 and 21 short arms in the left gonad [16]. Huang et al described a unique telomeric association involving the Y chromosome that “jumped” during meiosis from chromosome 19 in the father, tas(Y;19)(pter;pter), to chromosome 15 in his son, tas(Y;15)(pter;pter).…”

Section: Discussionmentioning

confidence: 99%

A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia

Zhang

Cooley

Chandratre

et al. 2013

Case Reports in Endocrinology

View full text Add to dashboard Cite

Disorders of sex development (DSD), formerly termed “intersex” conditions, arise from numerous causes. CAH secondary to 21-hydroxylase deficiency is the most common cause of DSD. Sex chromosome disorders, including sex chromosome mosaicism, are the second most common cause of DSD. We discuss a medically complex neonate with DSD presenting with ambiguous genitalia. Hormone levels suggested 21-hydroxylase deficiency. Molecular analysis revealed compound heterozygous mutations in the 21-hydroxylase gene (CYP21A2), confirming the diagnosis of CAH. Chromosome analysis revealed sex chromosome mosaicism with three cell lines: 45,X[8]/45,X,tas(Y;16)(p11.32;p13.3)[8]/45,X,t(Y;8)(p11.32;p23.3)[4] with the Y chromosome in telomere association with chromosomes 8p and 16p in different cell lines, a “jumping translocation.” Histologically, the right gonad had irregular, distended seminiferous tubules with hyperplastic germ cells contiguous with ovarian stroma and primordial follicles. The left gonad had scant ovarian stroma and embryonic remnants. Chromosome analyses showed mosaicism in both gonads: 45,X[17]/45,X,tas(Y;8)(p11.32;p23.3)[3]. This is the first case of coexisting CAH and 45,X/46,XY mosaicism reported in the English literature and the third case of a constitutional chromosome Y “jumping translocation.” Our report documents the medical and genetic complexity of children such as this one with ambiguous genitalia and discusses the need for a multidisciplinary team approach.

show abstract

Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

Cited by 11 publications

References 17 publications

Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome

Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome

Constitutional telomeric association (Y;7) in a patient with a female phenotype

A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia

Contact Info

Product

Resources

About