Sperm segregation patterns by fluorescence in situ hybridization studies of a 46,XY,t(2;6) heterozygote giving rise to a rare triploid product of conception with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype.
A blighted ovum diagnosed initially by ultrasound was determined to be a partial hydatidiform mole with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype by cytogenetic analysis. The triploid state arose through dispermy in which both spermatozoa carried rearranged chromosomes, one carrying a balanced translocation through alternate segregation and the other an unbalanced derivative chromosome 6 through adjacent 1 segregation. Segregation analysis of 7,000 spermatozoa from the father was performed with a three-color fluorescence in situ hybridization (FISH) protocol using alpha-satellite 6, telomeric 2p, and telomeric 6q probes. Segregation frequencies of normal and balanced products (alternate segregation), adjacent 1, adjacent 2, and 3:1 were 49.9%, 42.4%, 2.5%, and 4.2%, respectively. The high percentage of alternate segregation is consistent with the knowledge of their preferential outcome. However, the high incidence of adjacent 1 sperm highlights the abnormality risk. Alternate and adjacent 1 segregations (92.3%) accounted for the observed rearranged chromosomes in the triploid. The most viable imbalanced combination would be the one carrying the der(6) chromosome, but since the unbalanced segment comprises 3.6% of the haploid autosomal length (HAL), no risk of a viable imbalanced offspring is indicated. However, an increased likelihood of recurrent miscarriages is likely, and this is confirmed by the couple's two earlier miscarriages. Sperm segregation patterns of translocation carriers determined by FISH can help in ascertaining expected and unexpected karyotypes. The high frequency of adjacent 1 products shows that the presence of the additional derivative chromosome in the partial mole, though rare in occurrence, should be less surprising.
Lim
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AS
Department of Pathology, Singapore General Hospital, Singapore. stalvinlim@hotmail.com
Lim
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Kee
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Chieng
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Tay
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D000782:Aneuploidy; D002871:Chromosome Banding; D020090:Chromosome Segregation / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000473:pathology; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D011247:Pregnancy; D013094:Spermatozoa / Q000378:metabolism*; D014178:Translocation, Genetic; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology