To the Editor:
We thank Collins and Schimke for their letter adding to the discussion of loci that predispose to cancer that can be detected by microarray analysis with the addition of the deletion of 2p16.2p21 that includes SIX3, MSH2, and MSH6. At the time of our publication,1 we had not yet identified any patients with MSH2 or MSH6 deletions. Since then, we have encountered three patients with deletions including one or both of these Lynch syndrome genes. One case involved a fetus with holoprosencephaly, in whom microarray analysis identified a 17.6 Mb deletion encompassing SIX3, MSH2, and MSH6. The other two patients had smaller deletions (192 kb and 537 kb) encompassing only MSH6 and a neighboring gene, FBXO11. Both patients with smaller deletions had developmental delay and dysmorphic features; so while testing identified cancer predisposition in both, it is unclear if these deletions are the cause of their developmental features.
The Collins and Schimke case is another valuable example of a condition that can be identified by microarray analysis that requires specialist involvement beyond the neurologist, geneticist, or perinatologist who may have referred the case for testing. Their case nicely illustrates that a specific clinical action or decision may be dictated by the particular alteration identified. Microarray analysis can also detect conditions in addition to cancer predisposition that require specific clinical actions. These conditions include, among others, some forms of inherited cardiac arrhythmia2 (e.g., OMIM# 613688); renal anomalies and diabetes3 (OMIM# 137920); a form of thrombocytopenia4 (OMIM# 188025); and deafness5 (OMIM# 193500). As microarray testing becomes increasingly used in assessing patients with developmental abnormalities, its ability to alert physicians to unanticipated and actionable clinical problems is becoming more evident. The end results are more appropriate medical management and improved patient outcomes.
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Morton, S., Coppinger, J., Ballif, B. et al. Response to the letter by Collins and Schimke. Genet Med 13, 982–983 (2011). https://doi.org/10.1097/GIM.0b013e31823552be
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DOI: https://doi.org/10.1097/GIM.0b013e31823552be
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