American Journal of Medical Genetics 135A:86–90 (2005) Clinical Report An Unusual Reciprocal Translocation Detected by Subtelomeric FISH: Interstitial and Not Terminal Mariluce Riegel, 1 * Alessandra Baumer, 1 Jochen Su¨ ss, 2 and Albert Schinzel 1 1 Institute of Medical Genetics, University of Zuerich, Schwerzenbach, Switzerland 2 Klinikum St. Marien, Frauenklinik, Amberg, Germany An 11-month-old boy with a pattern of dysmorphic signs, an atrial septal defect, right inguinal hernia, bilateral undescended testes, bilateral urinary reflux, right renal dysplasia, and devel- opmental delay had an abnormal chromosome 11 with additional material of unknown origin attached to the long arm in his karyotype. The paternal karyotype was normal 46,XY, while the mother’s karyotype was 46,XX,t(2;11)(q35;q24.2). Thus, a reciprocal terminal exchange was assumed resulting in duplication of distal 2q material and a small subterminal 11q deletion. However, application of subtelomeric fluores- cence in situ hybridization (FISH) probes indi- cated that the translocation was not a terminal reciprocal exchange, but was interstitial at least for one of the chromosomes, which would be highly unusual since most interstitial transloca- tions are non-reciprocal. Based on the results of FISH and microsatellite marker examinations, the designation of the breakpoints and thus of the deleted and duplicated segments had to be revised. The findings have implications for kar- yotype-phenotype correlation. ß 2005 Wiley-Liss, Inc. KEY WORDS: interstitial translocation; subte- lomeric regions; duplication 2q/ deletion 11q INTRODUCTION If an unbalanced structural chromosome aberration is found in a child with malformations, and subsequent examinations of the parents disclose a balanced translocation involving a reciprocal exchange of chromosomal segments in one of them, duplication-deletion of distal segments extending to the telomeres is generally assumed. The mechanisms by which terminal deletions are generated and/or stabilized is not yet well understood. It has been shown that pure terminal deletions can be stabilized by telomere healing with telomeric repeat sequences or by a wide range of subtle telomeric rear- rangements. A number of reports [Bosco and Haber, 1998; Flores-Rozas and Kolodner, 2000; Daniel et al., 2003; Ballif et al., 2004] suggest that break-induced replication (BIR) at the site of a double-strand break may act as a mechanism of telomere capture by generating non-reciprocal translocations from terminally deleted chromosomes. We observed a patient with maternally inherited duplication of distal 2q and deletion of distal 11q; however, fluorescence in situ hybridization (FISH) with subtelomeric 2q and 11q probes showed that the rearrangement was more complicated and led to aneuploidy of interstitial segments. We describe an unusual interstitial reciprocal translocation detected by subtelomeric FISH. CLINICAL REPORT The propositus, a male (Fig. 1), is the product of the first pregnancy of a 29-year-old healthy and normal mother. Her sister who is 4 years younger is said to be mentally retarded with clubfeet and renal disease, but no further informations about her clinical findings could be obtained. The proband’s parents are second degree cousins: their grandmothers are sisters. The pregnancy was reported as normal, and spontaneous vertex delivery with vacuum extraction occurred at 37 þ 5 weeks. Apgar values were 5, 7, and 8 after 1, 5, and 10 min, respectively. During the first postnatal day, he required oxygen and had periods of tachypnea. He showed a large cephalhematoma and bilaterally undescended testes. Birth measurements were: weight 3,540 g (about 75th centile), length 52 cm (almost 90th centile), OFC 33.5 cm (50th centile). At age 1 week, a pediatrician noticed several dysmorphic signs and requested a chromosome examination. Subsequent ultrasonographic examinations showed small kidneys with dilated left renal pelvis, and normal hearing. At 6 weeks of age, he was hospitalized because of pyelonephritis. Examinations showed a hypo-dysplastic and almost non-functioning right kidney and vesico-ureteral reflux of 3rd grade on the right and of 4th grade on the left side. His voice was described as high- pitched. Feeding did not cause any difficulty. Cardiac exam- ination showed an atrial septal defect type II and a chord running through the left ventricle. At age 2½ months, right inguinal hernia was operated on and at that occasion the right testis was placed into the scrotum. At that time, muscular hypotonia, poor head control, and eczema were noticed. The anterior fontanel closed prematurely at age 7 1 / 2 months. He received physiotherapy. At age 2 1 / 12 years, a further operation aimed to bring the testes into the scrotum was performed, but the left testis could not be found any more. Clinical examination at age 10 months: length 73.5 cm (50th centile), weight 8.15 kg (10th–25th centile), OFC 42.5 cm (<3rd centile). Further measurements: ear length 5.0 cm (75th centile), ICD 3.1 cm (>97th centile), hand length 9.0 cm (50th centile), foot length 11.0 cm (25th centile). The following dysmorphic findings were observed (in parentheses: occurrence among six patients with duplication of 2q35 ! qter [Schinzel, 1994]): prominent occiput (1), narrow forehead (0), upslanting palpebral fissures (3), inner epicanthic Grant sponsor: ECARUCA Project of the European Counsil; Grant number: QLRT-2001-02746; Grant sponsor: Suiss Project; Grant number: 03.0015. *Correspondence to: Mariluce Riegel, Ph.D., Institute of Medical Genetics, University of Zu¨ rich, Schorenstrasse 16, CH- 8603, Schwerzenbach, Switzerland. E-mail: riegel@medgen.unizh.ch Received 17 September 2004; Accepted 18 February 2005 DOI 10.1002/ajmg.a.30683 ß 2005 Wiley-Liss, Inc.