Bateman M.S.,Salisbury District Hospital |
Mehta S.G.,Addenbrookes NHS Trust |
Willatt L.,Cambridge Regional Cytogenetics Laboratory |
Selkirk E.,Cytogenetics Laboratory |
And 6 more authors.
American Journal of Medical Genetics, Part A | Year: 2010
Cytogenetically visible imbalances without phenotypic effect are still rare despite the extent of large-scale copy number variation in the normal population revealed by array CGH. Here we report on a phenotypically normal 30-year-old female with a de novo, cytogenetically visible, interstitial deletion of band 4q34. She was referred following three successive miscarriages, one of which was an intra-uterine death with subendocardial fibroelastosis and dilated cardiomyopathy. There was no other notable medical or family history, she was of normal intelligence and had no dysmorphic features. FISH and Array CGH with a customized 1Mb BAC array showed that the deletion is aminimumof 9.3 and a maximum of 10.7Mb in size, between ∼173 Mb in 4q34.1 and ∼182 Mb in 4q34.3. The deletion contains only 23 known coding genes giving a lowaverage gene density of ∼2 genes/Mb. This case further illustrates that (1) sizeable imbalances can be associated with apparent phenotypic normality, (2) gene density is a better guide to possible phenotypic consequences than aberration size, and (3) it is not always safe to assume that de novo imbalances will be causal. © 2010 Wiley-Liss, Inc.