Use of Array Comparative Genome Hybridization in Orofacial Clefting

Abstract

Orofacial clefting is a common condition found in 1 per 700 to 1 per 1000 births. Although most cases are isolated, a subset is caused by a specific genetic mutation. Specific gene tests have been used for recognizable syndromes such as velocardiofacial syndrome or van der Woude syndrome, where the cleft is associated with other anomalies. However, many cleft lip and palate patients have other anomalies but do not fit in to a recognizable syndrome. For these patients, chromosome analysis has been a first-line genetic test; however, in the past few years, a new form of genetic testing has become available for these patients: array comparative genome hybridization (aCGH). We present a 7-month-old male infant with cleft palate, developmental delay, and a family history of velopharyngeal insufficiency in whom aCGH array was used to identify a small deletion on the short (p) arm of chromosome 7. This defect, which was also found in the mother, was undetected by chromosome analysis. In summary, this case demonstrates that aCGH is a new diagnostic tool that is useful in the evaluation of select cases of orofacial clefting. Array comparative genome hybridization should be considered when the suspicion for a genetic etiology of the clefting remains strong despite a normal cytogenetic analysis.

Delineation of a less than 200 kb minimal deleted region for cardiac malformations on chromosome 7p22

“…Recently, Gallego et al reported a 7-month-old male with a VSD who had a maternally inherited microdeletion of 7p which extended from approximately 2.19-5.08 Mb (hg18) and contained 20 genes [Gallego et al, 2010]. The distal breakpoint of this deletion is also located in MAD1L1 but is approximately 200 kb proximal to the breakpoint seen in our patient.…”

“…The deletion included all, or portions, of the coding regions of four genes-MAD1L1, FTSJ2, NUDT1, and SNX8-and may also interfere with the normal expression of EIF3B by deleting upstream regulatory elements. These genes are also included in the less than 200 kb minimal deleted region for cardiac malformations that can be defined using data from this patient and the proband reported by Gallego et al who had a VSD [Gallego et al, 2010]. None of these genes have been previously implicated in the development of cardiac anomalies.…”

“…with individual genes shown as block arrows. The extent of the deletion seen in our patient and the $2.9 Mb deletion described by Gallego et al in a child with a VSD are represented by green bars [Gallego et al, 2010]. Vertical dashed lines mark the approximate location of the minimal deleted region for cardiac malformations defined using the distal breakpoint of the deletion described by Gallego et al and the proximal breakpoint of the deletion seen in our patient (hg18 $2,190,000 and 2,366,962).…”

“…Craniosynostosis has been a central focus of much of the research involving deletions of 7p-with mutations in the TWIST1 gene on 7p21 and GLI3 on 7p13 being implicated in its formation [Wild et al, 1997;Seto et al, 2007]. Individuals with isolated terminal deletions distal to TWIST1 do not have craniosynostosis but can have cardiac malformations [Speleman et al, 1989;Gallego et al, 2010]. The identity of the gene, or genes, responsible for these malformations has yet to be identified.…”

High-Resolution Array Comparative Genomic Hybridization Utility in Polish Newborns with Isolated Cleft Lip and Palate

“…The use of microarray technology provides an opportunity for an accurate molecular characterization of the identified CNVs, and thus identification of candidate genes for NSCL/P [21]. The development of modern molecular genetics resulted in selecting about 10 genes of major effect in CL/P formation [22].…”