A familial unbalanced subtelomeric translocation resulting in monosomy 6q27→qter

Subtelomeric rearrangements have recently gained considerable interest through publications indicating that they may be a major cause for unexplained mental retardation and/or multiple congenital anomalies.1,2 As the subtelomeric regions have the highest gene density in the genome,3 subtelomeric aneusomies are in general thought to have a significant effect on the phenotype. Prenatal onset of growth retardation, a positive family history of mental retardation, and malformations have been discussed as being typically associated with subtelomeric defects.4 Here, we describe a family in which an unbalanced subtelomeric rearrangement segregated through at least two generations. The imbalance was caused by two rearranged chromosomes, a der(6)(6pter→6q27::16p13.12→16pter) and a del(16)(:p13.12→qter), which resulted in monosomy 6q27→qter. In these affected family members the monosomy caused very mild mental retardation without specific dysmorphic features. However, one family member with multiple congenital anomalies was a carrier of the der(6)(6pter→6q27::16p13.12→16pter) together with two normal copies of chromosome 16, which resulted in trisomy 16pter→p13.12 in addition to the partial monosomy 6q. As the consequences of the 6q aneusomy on the phenotype were surprisingly mild, we decided to fine map the deleted region and to determine accurately the number of lost genes. The same was done for the 16p region. This case should contribute to a better phenotype-genotype correlation for the distal region of both the long arm of chromosome 6 and the short arm of chromosome 16. The pedigree of the family is shown in fig 1. Figure 1 Pedigree and hybridisation results obtained with subtelomere PACs for 6q (shown in red, clone name 57H245) and 16p (shown in green, clone name 119L166). Family members II.1, III.2, and III.5 show the same hybridisation pattern with monosomy 6q. IV.5 had three signals for 16p and one signal for 6q. III.4 and IV.1 had normal hybridisation patterns on chromosomes …