title: Involvement of interstitial telomeric sequences in two new cases of mosaicism for autosomal structural rearrangements.
abstract: Mosaicism for an autosomal structural rearrangement that does not involve ring or marker chromosomes is rare. The mechanisms responsible for genome instability have not always been explained. Several studies have shown that interstitial telomeric sequences (ITSs), involved in some mosaic constitutional anomalies, are potent sources of genomic instability. Here we describe two cases of mosaicism for uncommon constitutional autosomal rearrangements, involving ITSs, identified by karyotyping and characterized by FISH and SNP-array analysis. The first patient, a boy with global developmental delay, had a rare type of pure distal 1q inverted duplication (1q32-qter), attached to the end of the short arm of the same chromosome 1, in approximately 35% of his cells. The second patient, a phenotypically normal man, was diagnosed as having mosaic for a balanced non-reciprocal translocation of the distal segment of 7q (7q33qter), onto the terminal region of the short arm of a whole chromosome 12, in approximately 80% of his cells. The remaining 20% of the cells showed an unbalanced state of the translocation, with only the der(7) chromosome. He was ascertained through his malformed fetus carrying a non-mosaic partial monosomy 7q, identified at prenatal diagnosis. We show that pan-telomeric and subtelomeric sequences were observed at the interstitial junction point of the inv dup(1q) and of the der(12)t(7;12), respectively. The present cases and review of the literature suggest that the presence of ITSs at internal sites of the chromosomes may explain mechanisms of the patients's mosaic structural rearrangements.
authors.affiliation: Service de Génétique et Embryologie médicales, AP-HP, Hôpital Armand Trousseau, Université Paris VI, Paris, France; Département de génétique, AP-HP, Hôpital Robert Debré, Université Paris VII, Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lévy
authors.forename: Aline
authors.initials: A
authors.lastname: Receveur
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jedraszak
authors.forename: Sandra
authors.initials: S
authors.lastname: Chantot-Bastaraud
authors.forename: Florence
authors.initials: F
authors.lastname: Renaldo
authors.forename: Jean
authors.initials: J
authors.lastname: Gondry
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Henri
authors.initials: H
authors.lastname: Copin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Portnoï
mesh_terms: D000328:Adult; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide; D016615:Telomere / Q000235:genetics*; D014178:Translocation, Genetic
keywords: SNP-array; autosomal structural rearrangement; interstitial telomeric sequences; mosaicism; non-reciprocal translocation; trisomy 1q