Submicroscopic terminal deletion of 1p36.3 and Xp23 hidden in complex chromosome rearrangements: Independent mechanism of telomere restitution on the two chromatids

• Published in: American journal of medical genetics 2003-03, Vol.117A (3), p.261-267
• Main Authors: Reddy, Kavita S., Yang, Xiaojing
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromatids - genetics; Chromosome aberrations; Chromosome Deletion; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, X - genetics; complex rearrangements; Female; Fetus - metabolism; Humans; In Situ Hybridization, Fluorescence; Infant; Karyotyping; Medical genetics; Medical sciences; Models, Genetic; Telomere - genetics; telomere restitution; terminal deletions; Translocation, Genetic
• ISSN: 1552-4825; 0148-7299; 1552-4833; 1096-8628
• DOI: 10.1002/ajmg.a.10108

In this study, we report two cases each with a complex chromosome rearrangement concealing a submicroscopic terminal deletion. The first case had a mos 46,XX,der(1)t(1;9)(p36.3;p13). ish der(1)(wcp9 +, 1ptel−, 9ptel +, pan tel +)[88]/46,XX. ish del(1)(1ptel −, 9ptel −, pan tel +)[12] karyotype. Scrutiny by FISH using wcp 9, 1ptel, 9ptel, and pan telomeric probes found a subtelomeric 1ptel deletion on the der(1) in the abnormal cell line and on a chromosome 1 in the apparently normal cell line. The telomere (TTAGGG)n, however, was present on the terminal ends of both copies of chromosome 1 in the apparently normal and abnormal cell lines. The second case had a de novo mos 46,X,der(X)t(X;22)(p22.3;q11.2),inv dup(22)(q11.2).ish der(X)(wcpX +,wcp22 +,KAL +, STS −,Xptel −,BCR +),inv dup(22)(wcp22 +,TUPLE ++,BCR −)[85]/45,X,der(X)t(X;22)(p22.3;q11.2),− 22[15].ish der(X)(wcpX +,wcp22 +, KAL +,STS −,Xptel −,BCR +) karyotype. FISH probes identified a terminal Xpter deletion, distal to the KAL gene. The two rearrangements are hypothesized to have been initiated by a terminal deletion. We propose a model for the formation of the rearrangement in Case 1, which invokes independent telomere stabilization of the sister chromatids. A terminal deletion 1pter in meiosis, was followed by acquiring or regenerating a telomere (TTAGGG)n cap on one chromatid and the other chromatid was involved in a translocation with a chromosome 9 chromatid. Following segregation of this chromosome the viable cell line survives to form the mosaic karyotype. Our findings suggest that subtelomeric deletions should be ruled out in cases with complex and simple rearrangements involving the terminal regions. © 2003 Wiley‐Liss, Inc.