RESEARCH LETTER Constitutional Telomeric Dysfunction in an Azoospermic Male With Extensive Telomeric Association Iman Salahshourifar, 1 * Hamideh Karimi, 1 Tayebeh Tavakolzadeh, 1 Zahra Beheshti, 1 Toyoki Maeda, 2 Hana Aviv, 3 and Hamid Gourabi 1 1 Genetics Department, Reproductive Biomedicine Research Center, Royan Institute, ACECR, Tehran, Iran 2 Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Kyushu University, Beppu, Oita, Japan 3 Laboratory of Cytogenetics, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, New Jersey Received 26 July 2009; Accepted 14 February 2010 TO THE EDITOR: Chromosomal abnormalities that contribute to telomere dysfunc- tion belong to one of two categories: telomere associations (TAS) and jumping translocations (JTs). The term JT was first coined by Lejeune et al. [1979] to designate a translocation of the same chromosome segment to different recipient chromosomes in dif- ferent cell lines of a single individual. TAS refers to end-to-end fusion of human chromosomes, resulting in usually non-clonal dicentric chromosomes, and involves different chromosomes from cell to cell [de Lange, 1995]. JTs and TAS are rare chromosomal aberrations, usually identified in malignancies, and are relatively rare in constitutional cytogenetic studies [Ben-Neriah et al., 1991; Reis et al., 1991; Huang et al., 2004; Berger and Bernard, 2007]. We present a 33-year-old male with azoospermia and an unusual TAS involving chromosome 22 (donor chromosome), and at least 43 recipient sites in the genome. The abnormality most likely originated during embryogenesis. The patient’s medical history was significant for bilateral congenital cataracts and bilateral vari- cocele and history of thyroid disorders. There were no other remarkable findings in the family history. Sample collection and genetic study for each member of this family were performed with the informed consent obtained before evaluation. Chromosome analysis of cultured peripheral blood lympho- cytes and skin cells was performed using standard cytogenetic techniques. The entire chromosome 22, form the p satellite region to the q terminal, acted as the donor chromosome in 97% (613 of 631) of the patient’s leukocyte cells and was identified at the telomeric ends of 43 different chromosomes (Figs. 1 and 2). Apart from some subtle rearrangements and numerical changes, the karyotype of main recurrent abnormalities in peripheral blood was 46,XY,tas(11;22)(p22.3;p13)[453]/46,XY,tas(13;22)(p13;p13)[22]/ 46,XY,tas(11;22)(q25;p13)[17]/46,XY,tas(15;22)(p13;p13)[14]/46, XY,tas(14;22)(p13;p13)[11]/46,XY,tas(21;22)(p13;p13)[8]/46,XY,tas (Y;22)(p11. 32;p13)[8]. The main cell line (46,XY,tas(11;22) (p15.5;p13)) was identified in 72% (453 out of 631) of analyzed cells, and in 25% of cells (160 out of 631) chromosome 22 was seen at the telomeric regions of other chromosomes (Figs. 1 and 2). Of the remaining cells (18 of 631), 6 had a normal karyotype, 9 had aneuploidy of chromosome 22 (49,XY,þ22,þ22,þ22[1], 45, XY,22[7], 47,XY,þ22[1]), two cells had an unusual double TAS 46,XY,tas(3;14)(p26.3;p13),tas(11;22)(p15.5;p13), 46,XY,tas- (13;15) (p13;p13),tas(17;22)(p13.3;p13) and one cell had 46,XY,tas(16;22)(p13.3;q13.3) karyotype (Fig. 3). To confirm the observed chromosomal abnormality, conven- tional cytogenetic was performed on skin fibroblast cells. The main cell line was 46,XY,tas(11;22)(p15.5;p13), seen in 63% Grant sponsor: Genetic Department, Royan Institute, Tehran, Iran. *Correspondence to: Iman Salahshourifar, Genetics Department, Reproductive Research Center, Royan Institute, ACECR, P.O. Box 19395-4644, Tehran, Iran. E-mail: isalahshouri@gmail.com Published online 18 August 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.33411 How to Cite this Article: Salahshourifar I, Karimi H, Tavakolzadeh T, Beheshti Z, Maeda T, Aviv H, Gourabi H. 2010. Constitutional telomeric dysfunction in an azoospermic male with extensive telomeric association. Am J Med Genet Part A 152A:2413–2416. Ó 2010 Wiley-Liss, Inc. 2413