Four new cases of inverted terminal duplication: A modified hypothesis of mechanism of origin

Abstract

We present 4 recently diagnosed cases of inverted tandem duplication with involvement of the respective terminal band. Based on these 4 cases and review of the literature, the term "inverted terminal duplication" is proposed to designate specifically the type of inverted tandem duplication which involves the terminal band. A modification of the previous hypothesis of mechanism of origin is advanced. It is speculated further that a telomeric deletion of a meiotic chromosome followed by a U-type reunion of the chromatids, considered to be the first steps of the proposed mechanism of origin, may not be a rare gonadal event.

Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4

“…The homozygosity for paternal alleles within the duplicated region observed in the proposita and the patient of Stetten et al [1997] can be explained by a sister chromatid rearrangement (paternal meiosis-II or postzygotic origin). This observation, together with loss of subtelomeric sequences accounting for only a single parental allele, is consistent with the model proposed by Hoo et al [1995]. A simple two chromatid break, at meiosis-II or post-zygotically, and U-type reunion would generate an intermediate dicentric chromosome.…”

“…An unequal crossover at meiosis or unequal sister chromatid exchange at mitosis are the most likely mechanisms for tandem duplications [Breslau-Siderius et al, 1993;Cotter et al, 1997]. Various models were proposed for the origin of inverted duplications [Van Dyke, 1988;Feldman et al, 1993;Hoo et al, 1995;Floridia et al, 1996]. To date, the best characterized by molecular analyses were terminal inversion duplications of distal 8p.…”

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

“…17 An alternative mechanism may consist of a two-chromatid break, followed by a U-type reunion of the broken ends producing a dicentric intermediate chromosome that is rescued by subsequent random breakage and telomere healing. 21 Such an event, occurring during paternal meiosis, 22 may be underlying our case, as the abnormal chromosome is of paternal origin. Our patient highlights the complexity of clinical phenotypes in patients with chromosomal aberrations.…”

Severe Phenotype in a Girl with Partial Tetrasomy 7, Karyotype 46,XX,trp(7)(q35q36)

“…The boy was severely retarded with regard to psychomotor skills. A girl with apparently the same size duplication was reported by Hoo et al [1995;case 1]. She revealed posteriorly rotated ears, clubfeet, cleft palate, and severe micrognathia which led to respiratory problems.…”