that are represented in the kit. Very small deletions or duplications (within exons) will be
missed using MLPA analysis in general, but bigger copy number variations are detectable
with both MLPA kits.
The frequency of exon deletions in our cohort was 1.9% (1/54) and 5.6% (1/18) in all pa-
tients and in typical CHARGE patients, respectively. The latter ﬁgure is in accordance with
the ﬁnding of Udaka et al. However, it should be noted that the classiﬁcation of our CHARGE
patients is based on the available clinical information. Unfortunately in 42 patients imaging of
the semicircular canals has not been performed. This means that the 25 patients who satisﬁed
the Verloes’ criteria for atypical or partial CHARGE could in theory have typical CHARGE in
the presence of semicircular canal anomalies. If we take this precaution into account, the fre-
quency of partial CHD7 deletions in typical CHARGE patients without a mutation in CHD7 is
2.3e5.6% (1/43e1/18) according to our study.
Since we did not detect any exon copy number alterat ions in the 36 non-typical patients, it
seems that MLPA analysis of the CHD7 gene does not signiﬁcantly improve the mutation anal-
ysis for this group of patients. In typical CHARGE patients however, we do recommend MLPA
analysis of the CHD7 gene, even though the frequency of partial CHD7 deletions is low. A thor-
ough clinical work-up is essential (e.g. imaging of semicircular canals) in order to classify pa-
tients as typical or non-typical CHARGE patients.
We thank Jackie Senior for her help in preparing this manuscript. Dr. Bergman was sup-
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