Prenatal Evaluation of a Fetal Cystic Hygroma: An Unexpected Finding of a De Novo Fetal BRCA1 Deletion Case Report

Round 1

Reviewer 1 Report

The manuscript by Laniewski et al presents a case report describing prenatal evaluation of a fetal cystic hygroma. During evaluation a chromosome analysis showed, in addition to a normal karyotype, an 80-kb deletion on 17q21.31. This region contains a the gene BRCA 1 and further analyses showed this as a de novo fetal deletion.

Manuscript is well written and fits in the classification of a Case Report that would add to our knowledge of the molecular alterations observed in fetal cystic hygromas.

Minor

Define abreviation CNV at first mention (line 130)

Author Response

Thank you very much for taking the time to review our manuscript. We agree the abreviation CNV at first mention (line 130) needed to be defined. We have defined the abreviation CNV at first mention (line 130). 

Reviewer 2 Report

"Prenatal evaluation of a fetal cystic hygroma: an unexpected finding of a de novo fetal BRCA1 deletion case report" is a report of "incidental" finding of a BRCA1 gene deletion determined by microarray analysis. Although the reviewer is not a native speaker , there seems some serious problems. Besides, authors call the microarray analysis  as "reflex" test. In a well-determined genetic diagnosis algorithm, nothing may be called as a "reflex" . As there is any literature reporting the association between cystic hygroma and BRCA1 deletion, it is important to to exclude all other possible conditions that may be related to cystic hygroma, according to my opinion. For example, noonan syndrome and rasopathy related mutation screening may be offered as rapotahies are a quite common cause of CH. 

Author Response

We appreciate the reviewers feedback.  It is common practice in our region to order a karyotype and proceed to microarray only if the karyotype is normal.  This is referred to as “reflex” testing and is a normal practice.  Other tests are handled very similarly like a reflex urine culture.  This practice is used for efficiency and cost savings.  To the latter point, this is not a case report to detail the evaluation and mangement of a cystic hygroma as that is well established and would not be case reportable.  Nor do we insinuate the the cystic hygroma is in any way related to BRCA1.  Rather this is a report discussing the implications of identifying a BRCA1 deletion “incidentally” in the process of evaluating a cystic hygroma.

A sentence was added to the discussion to clarify this point.

Reviewer 3 Report

 Prenatal Evaluation of a Fetal Cystic Hygroma: An Unexpected  Finding of a de novo Fetal BRCA1 Deletion Case Report is a very interesting case for the Society of Clinical Genetics and I have no comments on this manuscript.

Author Response

Thank you very much for taking the time to review our manuscript.