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We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.

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We describe a duplication of the 8p23.2 band in seven individuals from four families. The duplication was recognizable as an enlarged 8p23.2 band on G-banded chromosomes at the 550 band level. It was transmitted from a parent to offspring in three of the four families in which both parents were karyotyped. Each proband in the four families had the enlarged band and showed various phenotypic abnormalities, but the abnormalities were inconsistent. Chromosomal and interphase fluorescence in situ hybridization (FISH) analysis of the enlarged band region defined a 2.5-Mb duplicated segment common to all seven individuals studied. Interphase FISH analysis of peripheral blood lymphocytes from 50 unrelated normal individuals showed the duplication in three individuals. In view of these findings, it is most likely that the 8p23.2 duplication we described is a normal variant.

We describe two new cases of pure 1q terminal deletions. BAC FISH analysis precisely defined the size of deletions. The first is a girl with 10.3-Mb deletion showed typical features of 1q43 deletion as well as a simplified gyral pattern, which was rarely found in 1q43 deletion. The other boy also presented with most of 1q43 deletion features but several atypical symptoms were noted including hydrocephalus, adducted thumbs, and flexion restriction of proximal interphalangeal joints in left hand. A concomitant novel missense mutation in L1CAM was identified in addition to 11.5-Mb deletion. Reviewing all the cases of pure 1q terminal deletion in the literature suggests that it is a clinically recognizable syndrome.