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

Abstract

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.

A Turner syndrome case associated with dic(Y;22)

“…Thus, we speculated from our current findings for this patient that the original dic(Y;22) chromosome was generated by unstable TAs. Since similar SNP microarray data were also previously reported for tas(Y;7), the mosaicism in our present patient is likely to have arisen via the latter process [ 3 ]. We hereby propose a novel “pulled apart” mechanism which is caused by TA fragility and that leads to this unique mosaicism.…”

“…We here report a patient with possible TA between chromosomes Y and 22 manifesting a Turner syndrome phenotype. Four cases with TAs involving an autosome and chromosome Y have been reported to date (Table 1 ) [ 3 – 5 , 13 ]. All of these prior cases involve a mosaicism of cell lines with TA and with 45,X, suggesting the instability of the TA chromosome, resulting in a Y chromosome loss.…”

“…Thus, the telomere sequence at the junction of a TA may be too short to be detectable by telomere FISH. Notably in this regard, some reported TA cases show positive telomere FISH signals while others do not [ 3 , 5 ].…”

“…A considerable subset of Turner syndrome cases develop as a 45,X mosaicism [ 11 , 12 ]. Previously reported cases involving TAs between the Y chromosome and the autosomes manifested a phenotype involving a mixed gonadal dysgenesis due to Y chromosome loss (Table 1 ) [ 3 – 5 , 13 ]. Since the mosaic ratio varies among patients, and also varies from tissue to tissue, some cases manifested mixed gonadal dysgenesis and others manifested a Turner phenotype.…”

“…Cases with TAs involving an autosome and chromosome Y have been occasionally reported. Cases of constitutional TAs between an autosome and chromosome Y have been generally reported as a mosaicism of two cell lines: a line with an end-to-end fusion of the Y and autosomal chromosomes, resulting in a dicentric chromosome, and a line whereby the dicentric chromosomes have been separated from each other and only the Y chromosome is lost [ 3 , 5 ]. It is possible that the repeated TAs between an autosome and Y chromosome described in prior reports have been based on the recognizable Turner syndrome phenotype arising after the loss of the Y chromosome.…”