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A genome-wide study of de novo deletions identifies a candidate locus for non-syndromic isolated cleft lip/palate risk

14 Feb 2014

Background:
Copy number variants (CNVs) may play an important part in the development of common birth defectssuch as oral clefts, and individual patients with multiple birth defects (including clefts) have beenshown to carry small and large chromosomal deletions. In this paper we investigate de novo deletionsdefined as DNA segments missing in an oral cleft proband but present in both unaffected parents.We compare de novo deletion frequencies in children of European ancestry with an isolated, nonsyndromicoral cleft to frequencies in European ancestry children from randomly sampled trios.
Results:
We identified a genome-wide significant 62 kilo base (kb) non-coding region on chromosome 7p14.1where de novo deletions occur more frequently among oral cleft cases than controls. We also observedwider de novo deletions among cleft lip palate (CLP) cases than seen among cleft palate (CP) and cleftlip (CL) cases.
Conclusions:
This study presents a region where de novo deletions appear to be involved in the etiology of oralclefts, although the underlying biological mechanisms are still unknown. Larger de novo deletions aremore likely to interfere with normal craniofacial development and may result in more severe clefts.Study protocol and sample DNA source can severely affect estimates of de novo deletion frequencies.Follow-up studies are needed to further validate these findings and to potentially identify additionalstructural variants underlying oral clefts.

Date: 
14 February 2014

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