Prenatal detection of subtelomeric rearrangements by multi‐subtelomere FISH in a cohort of fetuses with major malformations

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Abstract
Cryptic unbalanced subtelomeric rearrangements have been identified as an important contributor (∼6%) to the etiology of mental retardation and dysmorphism. Our objective was to study the role of these rearrangements in the development of fetal malformations. Multi‐subtelomere FISH was performed on cells from 48 fetuses with major malformations diagnosed by prenatal ultrasound with a normal karyotype at a minimal 400 band resolution. We developed a method of performing multi‐subtelomere FISH on a single slide of amniocyte metaphase spreads. We identified five subtelomeric abnormalities: two derivative chromosomes inherited from a parent carrying a balanced translocation, two known polymorphisms, and one novel familial variant. These results show a similar frequency (4%) of clinically significant subtelomeric rearrangements to that found in children with multiple malformations. This study adds to a growing number of reports of cryptic subtelomeric rearrangements associated with congenital malformations and highlights the relevance and technical feasibility of multi‐subtelomere FISH screening of prenatal samples.