Polymorphic subtelomeric deletion 1q demonstrates the need to reevaluate subtelomere screening methods: Determination of the boundary between pathogenic deletion and benign variant for subtelomere 1q

It is undeniable that the different subtelomere screening methods for the detection of cryptic aberrations and rearrangements in the subtelomeric regions, which harbor the highest gene concentration in the human genome [Saccone et al., 1992] represent important and useful diagnostic approaches in testing patients with idiopathic mental retardation and/ or congenital malformations and dysmorphic features. Additionally, these diagnostic methods should be used in cases with broader implications like recurrent miscarriages and reduced fertility, that is, in patients who do not meet the criteria formulated in the checklist of De Vries et al. [2001]. With the establishment of the subtelomere investigations, the majority of screening studies were based on selected populations of patients with mental retardation. This preselection implies the problem of biased ascertainment and hampers the differentiation between pathogenetic rearrangements and benign variants. Only a few reports of systematic screening of phenotypically normal propositi using subtelomere probes have been published so far. By a study analyzing 11,688 cases out of a large, unselected population this problem could be minimized [Ravnan et al., 2006]. In this unbiased study, the detection rate for clinically significant subtelomere abnormalities was approximately 2.5%, with an additional 0.5% detection rate of presumed familial variants, coming to the conclusion that 20% of the findings presented telomere length polymorphismsor benign variants. We present the clinical, cytogenetic and molecular data of a healthy woman and her mother with an unusual translocation (1/13) resulting in a terminal deletion 1q (there was no detectable imbalance of genomic material of chromosome 13 except the tolerable deletion of the pericentric region of chromosome 13): the exact location of the breakpoint was delineated and the presentation of an inconspicuous phenotype is discussed in meaning of a phenotypic discordance or a polymorphism. We report on a 38-year-old female of normal intelligence with a history of two miscarriages followed by fertility problems in the previous 30 months. Clinical investigations revealed neither dysmorphic signs nor malformations. Chromosome analysis was performed because of recurrent miscarriages and reduced fertility. Our proposita is the only child of a healthy nonconsanguineous couple. The family history was positive for a further miscarriage of the patient’s healthy mother as well as for further stillbirths in other descendants of the family. Microsatellite marker analyses of material of the second abortion of our index patient revealed a trisomy 13 (data not shown). Chromosome studies were performed at a 400– 550 GTG-band-level (ISCN 2005) on peripherial blood lymphocytes of the patient and her parents, using standard procedures. The cytogenetic investigation revealed an unusual apparently unbalanced translocation 45,XX,t(1;13)(q44 or qter; q11) in the patient and her mother (Fig. 1). Both karyotypes