Authors' response to: The clinical utility and indications of chromosomal microarray analysis in prenatal diagnosis


Authors’ Reply


We thank Mr Alesi1 for his comments on our article.2 We reported a series of 3171 prenatal DNA samples analysed with chromosomal microarray analysis (CMA) for a wide range of heterogeneous indications, using different resolutions (1-Mb BAC microarray or 0.5-Mb oligonucleotide), regardless of indications. We used BAC microarray in the beginning because of the availability and the accumulating copy number variation database. Five cases were classified as variation of unknown clinical significance (VOUS): four detected by BAC microarray (4/2497, 0.16%) and one by oligonucleotide array (1/674, 0.14%). The oligonuclotide array did not identify more VOUS than the BAC microarray because the design of the probes of the two array platforms both targeted known microdeletion/duplication syndromes, avoiding the known copy number changes.

Mr Alesi claimed that the diagnostic value of CMA in our cohort of pregnancies should be adjusted to 0.36% (7/1911) in the advanced maternal age group and 0.2% (2/989) in the parental anxiety group. Although the 17p12 microdeletion (hereditary neuropathy with liability to pressure palsies, HNPP, syndrome) and 22q11.2 microduplication syndrome may have incomplete penetrance and variable expressivity, they are known clinical syndromes. Prenatal identification of these genetic changes indicates a detailed prenatal ultrasound examination and long-term clinical follow-up. In our cohort, 15 fetuses with normal karyotypes by conventional G-banding and normal prenatal ultrasound had microdeletion/duplication: that is, each pregnancy had a 5.2 per 1000, or a 1:192 risk for microdeletion/duplication. Although not all of the 15 fetuses will present with major physical anomalies at birth, prenatal diagnosis might provide more information for counselling and better prepare the parents for the possibility of giving birth to a child with impairment.

There is consensus for the application of CMA in fetuses with abnormal prenatal ultrasound findings, abnormal karyotyping or marker chromosomes. But more and more evidence suggests the merit of CMA in prenatal screening.3–5 Nevertheless, the interpretation and genetic counselling of CMA results in the prenatal setting is challenging, and the importance of this point cannot be overemphasized.