We report the prenatal diagnosis of an unbalanced translocation between chromosome Y and chromosome 15 in a female fetus. Cytogenetic analysis of parental chromosomes revealed that the mother had a normal 46,XX karyotype, whereas the father exhibited a 46,XY,der(15)t(Y;15) karyotype. We performed cytogenetic analysis of the father’s family as a result of the father and confirmed the same karyotype in his mother and brother. Fluorescence
Translocations involving the Y chromosome and an autosomal chromosome are very rare, occurring in approximately 1/2,000 of the general population. The most frequent translocation of this type occurs between the heterochromatin of the long arm of chromosome Y and the short arm of chromosome 15 [1,2]. This may be the result of a frequent sequence homology based association of the 15p and Yq heterochromatin, during the pachytene stage of male meiosis . The breakpoints are frequently located within the chromosome 15p11-15p13 and Yq11.23-Yq12 regions. These types of translocations are equally found in male and female patients, and carriers of t(Y;15) usually have a normal phenotype [2,4].
We report the prenatal diagnosis of an unbalanced translocation between chromosome Y and chromosome 15 in a female fetus, inherited from a paternal carrier. Molecular cytogenetic methods were used to cytogenetically characterize the der(15) translocation, and family history was helpful in prenatal counseling.
A 40-year-old pregnant woman was referred for amniotic fluid sampling at 16 weeks and three days due to advanced maternal age. Quantitative fluorescent polymerase chain reaction (QF-PCR) was performed in uncultured amniocytes using a set of short tandem repeat markers for chromosomes 13, 18, 21, X, and Y (Cybergene AB, Stockholm, Sweden). QF-PCR results revealed one abnormal pattern (X22) representing two pseudoautosomal regions PAR1 and PAR2 (X22 and DXYS218 ) (Fig. 1).
Cytogenetic analysis results showed the presence of additional material on the p-arm of one chromosome 15 (III-1 in Fig. 2). The karyotypes of the proband’s parents were examined to determine if this atypical chromosome 15 was inherited or occurred
We characterized the der(15) chromosome using fluorescence
In prenatal diagnosis, prediction of phenotypes caused by unknown chromosome fragments or translocations is big dilemma. Here, the unknown chromosome fragment identified during prenatal diagnosis was very confusing. However, QF-PCR results suggested that the abnormal chromosome related structural abnormality was found. QF-PCR is a very powerful tool for prenatal diagnosis of the most commoen aneuploidies. However, the detection of a trisomic pattern in only one marker, is more problematic. In such cases, parents should be tested to identify the presence of a duplication, and to rule out the possibility of partial trisomy. In the case of X22, heterochromatic Y chromosome material has already been described [5,6].
In this case, the translocation origin and breakpoints were determined through FISH using CEP 15, and Y specific probes. Our results demonstrate that standard karyotyping, in combination with FISH, is useful for the detection of rare chromosomal rearrangements. Some cases with Prader-Willi syndrome (PWS) exhibit translocations involving chromosome 15 with deletion of PWS regions [2,7-10]. However, by using CEP 15 (Fig. 3), we confirmed that the breakpoint in this case does not include the PWS region.
Accurate identification of der(15) chromosomal content during prenatal cytogenetic analysis may facilitate the prediction of the fetal phenotype. Therefore, characterizing the der(15) chromosome using FISH is recommended. The der(15)t(Y;15)(q12;p13) translocation identified in the present work is the most common form of Y-autosome translocation. While this karyotype appears unbalanced, examination of the family history and identification of the same chromosome in the paternal grandmother (I-1 in Fig. 2), reveals that the phenotype of the proband is predicted to be normal female.
Therefore we suggest that conventional cytogenetic methods, combined with molecular cytogenetic methods and family history, are very informative for prenatal diagnosis and prenatal genetic counseling.
Electrophoregram of prenatal diagnostic quantitative fluorescent polymerase chain reaction (QF-PCR; Cybergene AB, Stockholm, Sweden). A total of five short tandem repeats from chromosome 13 (D13S256, D13S303, D13618, D13S631, D13S634), five from chromosome 18 (D18S386, D18S391, D18S535, D18S858, D18S976), six from chromosome 21 (D21S11, D21S1411, D21S1412, D21S1413, D21S1435, D21S1444), three from chromosome X (DXS996, DXS1283, P39) and two from the pseudoautosomal regions PAR1 and PAR2 (X22 and DXYS218) were included.
Family pedigrees and cytogenetic characterization of the der(15) translocation.