DNA Polymorphism analyses in families with multiple recurrence of trisomy 21.

C. Pangalos (1), J.G. Lewis (2), J. Lejeune (1), S.E. Antonarakis (2).

Abstract form - American Society of Human Genetics ; Deadline for receipt: June 10, 1988


In order to investigate the parental origin of trisomy 21 in families with more than one child with free trisomy 21 , DNA polymorphism and cytogenetic analyses were performed.

Eight families with two or three trisomy 21 siblings per families were studied (families #01-#08). At least 100 blood lymphocytes from each parent were karyotyped. In only family #02 was mosaic of the paternal blood lymphocytes observed (3% trisomy 21 cells). DNA polymorphism analysis was performed in all members of these nuclear families using several single copy chromosome 21 specific DNA fragments as molecular probes. The parental origin of the additional chromosome 21 in all affected individuals has been determined. In each family the additional chromosome 21 in all affected siblings originated from the same parent. This result be explained by

(i) undetected mosaicism in the parent that contribued the additional chromosome 21 in more than offspring,

(ii) some unknown predisposing factor that causes recurrence of trisomy 21, or

( iii) chance alone. Undetected mosaicism (i) has been suggested to be the most common cause for multiple recurrence of trisomy 21 in siblings.

Three additional families (#09-#11) with two trisom 21 individuals who are second or third degree relatives were also studied. The results from DNA polymorphism analysis showed that the parents in whom the nondis junctions had occurred were not family relatives and, therefore, the finding of two trisomy 21 individuals in the pedigrees is attributed to chance.

In summary, the extra chromosome 21 originated in the same parent in families with two or more siblings with trisomy 21; however, in families with two non-first degree relatives with trisomy 21 the parents responsible for the trisomy were not blood relatives.