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In the parental study, height was measured to the nearest centimetre and weight was measured to the nearest kilogram.
These were all designated disadvantaged schools and this has contributed to the under-representation of the most vulnerable children in the parental study.
Based upon previous published recommendations [ 8, 13, 15], we had planned a priori to include the category of the parental study participant/respondent (mother versus father) as a variable in our regression model.
However, only 6 (6.1%) of the presently enrolled parental study participants and survey respondents were the patient's father, a number too small to allow for a valid assessment of the effect of the parental respondent in patient-parent HRQoL agreement.
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Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation.
Of the eight cases where parental studies were performed, all were found to be de novo.
Parental studies on the CNVs classified as VOUS in this study may enable clinical interpretation and provide valuable information for genetic counseling and the management of disease outcomes.
Also problematic is the limited sample size and lack of parental studies to exclude a CNV ostensibly associated with POI merely having been transmitted from a normal mother.
When parental studies were available, we identified those variants arising de novo and those inherited from a normal or phenotypically similar parent.
Further, for deletions and duplications, parental studies (by fluorescence in situ hybridization [FISH] or metaphase preparations, if possible) should be conducted to rule out the presence of a chromosomal rearrangement such as an insertion or inherited duplication.
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