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A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. In every group of chromosome abnormalities in the parents a predominance of female to male affected was noted (2:l). Approximately 50% of all chromosome abnormalities detected were balanced reciprocal translocations, 24%' were Robertsonian translocations, 12% wcre sex chromosomal mosaicisms in females, and the rest consisted of inversions and other sporadic abnormalities. Parents with two or more idiopathic pregnancy losses should be karyotyped to aid in management and counselling. When a translocation or other abnormality (e.g. X chromosomal mosaicism) predisposing to an abnormal zygote is found, prenatal diagnosis is indicated in future pregnancies. Even when parental karyotypes are normal, prenatal diagnosis should be considered in subsequent prcgnancies of parents with two or more pregnancy losses because of the high incidence of chromosome abnormalities in spontaneous abortions. For the same reason, if a single previous pregnancy loss is known to have been chromosomallp aneuploid, parental karyotypes may have to be examined (depending upon the finding in the pregnancy loss), and prenatal diagnosis should also be considered in subsequent pregnancies.Recurrent pregnancy losses, including spontaneous abortions, stillbirths and early neonatal deaths. are tragic events for the mother and family. Their causes often remain undetermined. They are frequently a reason for referral to obstetric and genetic units; in recent years such problems contributed over 5% of all referrals to our genetic clinics. %Deceased. 8 March 1985.Correspondence: A . 'r. 'I'harapel. Assistant Professor. Department of Pediatrics. University of TennesseeCcnter for the Health Sciences, 71 1 Jefferson Avenue. Memphis, T N 38163. USA. We a r e indebted t o our colleagues, William Dillon, Associate Professor of Obstctrics a n d Gynaecology, SUNY at Buffalo; R i c h a r d N. Anderson. Professor, a n d John V. D a c u s , Assistant Professor, M a t e r n a l a n d Fetal Division, D e p a r t m e n t of Obstetrics and Ciynaecology, UTCHS, and M a r i a n L. Rivas, Associate Professor of Pediatrics and C o m p u t e r Sciences, U T C H S , M e m p h i s , for criticism a n d stimulating discussion. T h i s w o r k w a s supported in part by t h e D H E W I M C J P r o j e c t No. 417. SUNY a t Buffalo and by t h e Genetics P r o g r a m C o n t r a c t No. R07-3232-21, Tennessee D e p a r tm e n t of H e a l t h and E n v i r o n m e n t . W e also t h a n k M a r y J. C h a r l t o n Allison and Jeanne C a t a l a n 0 for excellent secretarial help.

Duplications and deletions of the same gene loci or chromosome regions are known to produce different clinical manifestations and are significant factors in human morbidity and mortality. Extensive cytogenetic and molecular cytogenetic studies with cosmid and YAC probes in two patients with unique mosaicism for reciprocal duplication-deletion allowed us to further understand the origin of these abnormalities. The first patient’s mosaic karyotype was 46,XX,inv dup(11) (q23q13)/46,XX,del(11)(q13q23). The second patient had a 46,XY,dup(7)(p11.2p13)/46,XY,del(7)(p11.2p13)/46,XY karyotype. Fluorescence in situ hybridization studies on the first patient placed the two breakpoints near the folate-sensitive fragile sites FRA11A and FRA11B. The presence of repeated sequences responsible for these fragile sites may have been involved in the patient’s duplication-deletion. Our investigation leads us to conclude that, in addition to known mechanisms (such as unequal crossovers between homologs, unequal sister chromatid exchanges, excision of intrachromatid loops, and meiotic recombination within a single chromatid), duplication-deletion can also arise by the formation of an overlying loop followed by an uneven crossover at the level of the DNA strand.

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