Original ArticlesReview Article : Molecular Analysis to Assign Parental Origin and Distinguish De Novo i(2I q) From t(2I q2I q) in Two Down Syndrome Fetuses

Abstract

OBJECTIVE: We sought to determine the origin of two prenatal cases of chromosome 21 rear rangements not amenable to clarification by conventional cytogenetic methodology.

METHODS: Hypervariable repeat polymorphisms (chromosome 21) were used to determine the type of structural rearrangement and the parental origin of the rearranged chromosome. The repeats used were highly polymorphic and located very close to the centromere; thus, the likelihood of differences among the parental alleles and overall informativeness were increased.

RESULTS: The rea(21q21q) chromosomes were identified as a Robertsonian translocation in one fetus and an isochromosome in the other. The extra chromosome material was found to be maternal in origin in both cases.

CONCLUSION: The ability to clarify the origin of abnormal chromosomal rearrangements pro vides valuable information concerning possible mechanisms of aneuploidy, as well as clinical data that may have an impact in assessing a patient's risk for abnormal offspring. (J Soc Gynecol Invest 1994;1:128-30)

Keywords

Down syndrome chromosome rearrangement isochromosome Robertsonian translocation hypervariable repeat sequences.

Get full access to this article

View all access options for this article.

References

Darlington CD Misdivision and the genetics of the centromere . J Genet 1939;37:341-61.

Darlington CD The origin of iso-chromosomes. J Genet 1940;39:51-61.

de la Chapelle A. How do human isochromosomes arise? Cancer Genet Cytogenet 1982;5:173-9.

Shaffer LG , McCaskill C. , Haller V. , Brown JA , Jackson-Cook CK Further characterization of 19 cases of rea(21q21q) and delineation as isochromosome or Robertsonian translocations in Down syndrome. Am J Med Genet 1993;47:1218-22.

Schmutz SM , Pinno E. Morphology alone does not make an isochromosome. Hum Genet 1986;72:253-5.

Hecht F. The origin of isochromosomes. Clin Genet 1988 ; 33:318-9.

de Grouchy J. , Turleau C. Clinical atlas of human chromosomes . 2nd ed. New York: John Wiley & Sons, 1984.

Shulman LP , Raafat NA , Mace PC , et al. Significance of septations in isolated fetal cystic hygroma detected in the first trimester. Prenat Diagn (in press).

Warren AC , McInnis MG , Blaschak J. Dinucleotide repeat (GT)n markers on chromosome 21. Genomics 1992;14: 918-9.

10.

Burmeister M. , Cox DR , Myers RM Dinucleotide repeat polymorphism located at D21S120. Nucleic Acids Res 1990 ;18:4969.

11.

Van Camp G. , Backhovens H. , Cruts M. , et al. Identification of chromosome 21 DNA polymorphisms for genetic studies in Alzheimer's disease and Down syndrome . Hum Genet 1991;87:649-53.

12.

Sharana V. , Litt M. Tetranucleotide repeat polymorphism at the D21S11 locus. Hum Mol Genet 1992;1:67.

13.

Peterson MB , Schinzel AA , Binkert F. Use of short sequence repeat DNA polymorphisms after PCR amplification to detect the parental origin of the additional chromosome 21 in Down syndrome. Hum Genet 1991;48:65-71.

14.

Grasso M. , Giovannucci-Uzielli ML , Pierluigi M. , Tavellini F. , Perroni L. , Dagna-Bricavelli F. Isochromosome not translocation in trisomy 21q21q. Hum Genet 1989;84:63-5.

15.

Shaffer LG , Jackson-Cook CK , Meyer JM , Brown JA , Spence JE A molecular genetic approach to the identification of isochromosomes of chromosome 21. Hum Genet 1991;86:375-82.

16.

Antonarakis SE , Adelsberger PA , Petersen MB , Biokert F. , Schinzel AA Analysis of DNA polymorphisms suggests that most de novo dup(21q) chromosome in patients with Down syndrome are isochromosomes and not translocations. Am J Hum Genet 1990 ;47:968-72.

17.

Antonarakis SE , Peterson MB , McInnis MG The meiotic stage of nondisjunction in trisomy 21: Determination by using DNA polymorphisms . Am J Hum Genet 1992;50: 544-50.

18.

Peterson MB , Frantzen M. , Antonarakis S. Comparative study of microsatellite and cytogenetic markers for detecting the origin of the nondisjoined chromosome 21 in Down syndrome. Am J Hum Genet 1992;51:516-25.