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16p13.3 duplication associated with non-syndromic pierre robin sequence with incomplete penetrance.

Sun M, Zhang H, Li G, Wang X, Lu X, Sternenberger A, Guy C, Li W, Lee J, Zheng L, Li S - Mol Cytogenet (2014)

Bottom Line: To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region.The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies.Further studies of similar cases are needed to support our findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA ; Key Laboratory for Molecular Enzymology and Engineering, College of Life Sciences, Jilin University, Changchun, Jilin 130012 P. R. China.

ABSTRACT

Background: Pierre Robin sequence (PRS) is a condition present at birth. It is characterized by micrognathia, cleft palate, upper airway obstruction, and feeding problems. Multiple etiologies including genetic defects have been documented in patients with syndromic, non-syndromic, and isolated PRS.

Case presentation: We report a 4-year-old boy with a complex small supernumerary marker chromosome (sSMC) who had non-syndromic Pierre Robin sequence (PRS). The complex marker chromosome, der(14)t(14;16)(q11.2;p13.13), was initially identified by routine chromosomal analysis and subsequently characterized by array-comparative genomic hybridization (array CGH) and confirmed by fluorescence in situ hybridization (FISH). Clinical manifestations included micrognathia, U-type cleft palate, bilateral congenital ptosis, upslanted and small eyes, bilateral inguinal hernias, umbilical hernia, bilateral clubfoot, and short fingers and toes. To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region.

Conclusions: We suggest that the duplicated chromosome segment 16p13.3 possibly may be responsible for the phenotypes of our case and also may be a candidate locus of non-syndromic PRS. The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies. Further studies of similar cases are needed to support our findings.

No MeSH data available.


Related in: MedlinePlus

Confirmatory FISH result. Confirmatory FISH of this sSMC using centromere probe 14/22 (red) and TelVysion 16p (green) specific for 16pter revealed five distinct red signals and three distinct green signals confirming the origins of the sSMC. The marker is highlighted by a white arrow.
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Fig3: Confirmatory FISH result. Confirmatory FISH of this sSMC using centromere probe 14/22 (red) and TelVysion 16p (green) specific for 16pter revealed five distinct red signals and three distinct green signals confirming the origins of the sSMC. The marker is highlighted by a white arrow.

Mentions: Array CGH is the current standard assay used to determine the chromosomal origin and the genomic size of non-mosaic chromosomal imbalances such as this case. Unexpectedly, array CGH showed two different chromosomal segment gains: the first was the gain of 14q11.2 region with 3.8 Mb (19,694,999-23,534,999) and the second one was the gain of 16p13.13-pter region with 11.8 Mb (14,999-11,834,999) (GRCh36/hg18, UCSC Genome Browser, February 2006 Assembly) (Figure 2). To confirm that the two chromosomal segments, 14q11.2 and 16pter-p13.13, were indeed joined together to form the marker chromosome, confirmatory FISH testing, utilizing the centromeric probe 14/22 (red) and the TelVysion 16p probe (green) specific for 16pter, was performed. All the metaphase cells analyzed showed that the marker chromosome had both the centromeric signal of chromosome 14/22 (red color) and the subtelomeric signal of 16pter (green color) indicating this marker chromosome was indeed derived from the unbalanced translocation between chromosomes 14 and 16, der(14)t(14;16)(q11.2;p13.13) (Figure 3).Figure 2


16p13.3 duplication associated with non-syndromic pierre robin sequence with incomplete penetrance.

Sun M, Zhang H, Li G, Wang X, Lu X, Sternenberger A, Guy C, Li W, Lee J, Zheng L, Li S - Mol Cytogenet (2014)

Confirmatory FISH result. Confirmatory FISH of this sSMC using centromere probe 14/22 (red) and TelVysion 16p (green) specific for 16pter revealed five distinct red signals and three distinct green signals confirming the origins of the sSMC. The marker is highlighted by a white arrow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260201&req=5

Fig3: Confirmatory FISH result. Confirmatory FISH of this sSMC using centromere probe 14/22 (red) and TelVysion 16p (green) specific for 16pter revealed five distinct red signals and three distinct green signals confirming the origins of the sSMC. The marker is highlighted by a white arrow.
Mentions: Array CGH is the current standard assay used to determine the chromosomal origin and the genomic size of non-mosaic chromosomal imbalances such as this case. Unexpectedly, array CGH showed two different chromosomal segment gains: the first was the gain of 14q11.2 region with 3.8 Mb (19,694,999-23,534,999) and the second one was the gain of 16p13.13-pter region with 11.8 Mb (14,999-11,834,999) (GRCh36/hg18, UCSC Genome Browser, February 2006 Assembly) (Figure 2). To confirm that the two chromosomal segments, 14q11.2 and 16pter-p13.13, were indeed joined together to form the marker chromosome, confirmatory FISH testing, utilizing the centromeric probe 14/22 (red) and the TelVysion 16p probe (green) specific for 16pter, was performed. All the metaphase cells analyzed showed that the marker chromosome had both the centromeric signal of chromosome 14/22 (red color) and the subtelomeric signal of 16pter (green color) indicating this marker chromosome was indeed derived from the unbalanced translocation between chromosomes 14 and 16, der(14)t(14;16)(q11.2;p13.13) (Figure 3).Figure 2

Bottom Line: To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region.The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies.Further studies of similar cases are needed to support our findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA ; Key Laboratory for Molecular Enzymology and Engineering, College of Life Sciences, Jilin University, Changchun, Jilin 130012 P. R. China.

ABSTRACT

Background: Pierre Robin sequence (PRS) is a condition present at birth. It is characterized by micrognathia, cleft palate, upper airway obstruction, and feeding problems. Multiple etiologies including genetic defects have been documented in patients with syndromic, non-syndromic, and isolated PRS.

Case presentation: We report a 4-year-old boy with a complex small supernumerary marker chromosome (sSMC) who had non-syndromic Pierre Robin sequence (PRS). The complex marker chromosome, der(14)t(14;16)(q11.2;p13.13), was initially identified by routine chromosomal analysis and subsequently characterized by array-comparative genomic hybridization (array CGH) and confirmed by fluorescence in situ hybridization (FISH). Clinical manifestations included micrognathia, U-type cleft palate, bilateral congenital ptosis, upslanted and small eyes, bilateral inguinal hernias, umbilical hernia, bilateral clubfoot, and short fingers and toes. To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region.

Conclusions: We suggest that the duplicated chromosome segment 16p13.3 possibly may be responsible for the phenotypes of our case and also may be a candidate locus of non-syndromic PRS. The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies. Further studies of similar cases are needed to support our findings.

No MeSH data available.


Related in: MedlinePlus