Pericentric inversion of chromosome 4 giving rise to dup(4p) and dup(4q) recombinants within a single kindred.
Theoretically, every pericentric inversion can give rise, during meiosis, to 2 alternate recombinant chromosomes. One of these will have a duplication of short arm material and deletion of long arm material (dup p), and the other, a duplication of a long arm material and deletion of short arm material (dup q). However, most published cases have been limited to a single recombinant type occurring within a given kindred. Here we document a large pericentric inversion of chromosome 4 which gave rise, within 2 generations of a kindred, to both dup p and dup q recombinants. The family was ascertained by the birth of a baby girl with multiple congenital anomalies suggestive of Wolf-Hirschhorn syndrome, and was found to have a dup 4q recombinant. Subsequent studies of her father and of her 27-year-old mentally retarded aunt showed a balanced inv(4) (p15.32q35) and a dup 4p recombinant, respectively. Given that: (a) the balanced inversion involves approximately 87% of the length of chromosome 4; (b) the predicted meiotic pairing would be homosynapsis with loop formation; (c) the size of the segments distal to the breakpoints of the inversion are of similar and relatively small size; and (d) both recombinants are compatible with life, then the risk for recurrence of a recombinant in this family is high. Genetic counseling addressed these issues, and to date, both chronic villus sampling (CVS) and amniocentesis have been provided for prenatal diagnosis.
Hirsch
B
B
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
Baldinger
S
S
D000015:Abnormalities, Multiple / Q000235:genetics*; D007446:Chromosome Inversion; D002894:Chromosomes, Human, Pair 4; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D005810:Multigene Family; D010375:Pedigree