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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

Map of the chromosome 16p duplicated region. The order of the cases follows the same order in Table 2.
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Fig4: Map of the chromosome 16p duplicated region. The order of the cases follows the same order in Table 2.

Mentions: Chromosomal 16p is a common region for chromosomal rearrangements. Twenty-seven cases with pure 16p duplication characterized by array CGH or single nucleotide polymorphism (SNP) array assay were found in the literature and summarized in Table 2. Cytogenetically, twenty-six of them only involved band 16p13.3, and the remaining one involved the 16p13.2-16pter region, whereas our case had a gain of 16p13.13-pter region (Figure 4). Phenotypically, close review identified that in those twenty-seven cases, plus our case, twenty-four of them had documented mandible development and ten had micrognathia. The remaining four cases did not have mandible developmental description (Table 2, Figure 4). Based on current evidence, genomic microduplicaion syndromes are frequently associated with incomplete penetrance and variable expression of phenotypes [23]. In this cohort, ten out of twenty-four cases developed micrognathia, indicating that chromosome 16p duplication is the cause of micrognathia, although the penetrance was not complete. Etiologically, any factors resulting in micrognathia in the early development could lead to PRS. However, abnormal mandible growth early in development does not instantly trigger the subsequent events, such as cleft palate and/or glossoptosis. Some patients might have the isolated small jaw or cleft palate without the airway obstruction. Thus, in those patients who had micrognathia, a smaller number of patients with cleft palate was observed, and only our patient had both cleft palate and airway obstruction and was diagnosed with PRS. Previous studies documented that genetically, the specific gene mutations, translocations, deletions, and duplications involving multiple chromosomes related to PRS [1,4,16-19]. This evidence supported that PRS was a disease with genetic heterogeneity. The chromosomal or genetic anomalies were the initiating events of the whole PRS sequence. Therefore, the duplicated 16p13.13-pter region likely led to micrognathia and was also responsible for the PRS phenotype of our patient. At this time, the underlying causes promoting small mandible into PRS are not clarified.Table 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)

Map of the chromosome 16p duplicated region. The order of the cases follows the same order in Table 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Map of the chromosome 16p duplicated region. The order of the cases follows the same order in Table 2.
Mentions: Chromosomal 16p is a common region for chromosomal rearrangements. Twenty-seven cases with pure 16p duplication characterized by array CGH or single nucleotide polymorphism (SNP) array assay were found in the literature and summarized in Table 2. Cytogenetically, twenty-six of them only involved band 16p13.3, and the remaining one involved the 16p13.2-16pter region, whereas our case had a gain of 16p13.13-pter region (Figure 4). Phenotypically, close review identified that in those twenty-seven cases, plus our case, twenty-four of them had documented mandible development and ten had micrognathia. The remaining four cases did not have mandible developmental description (Table 2, Figure 4). Based on current evidence, genomic microduplicaion syndromes are frequently associated with incomplete penetrance and variable expression of phenotypes [23]. In this cohort, ten out of twenty-four cases developed micrognathia, indicating that chromosome 16p duplication is the cause of micrognathia, although the penetrance was not complete. Etiologically, any factors resulting in micrognathia in the early development could lead to PRS. However, abnormal mandible growth early in development does not instantly trigger the subsequent events, such as cleft palate and/or glossoptosis. Some patients might have the isolated small jaw or cleft palate without the airway obstruction. Thus, in those patients who had micrognathia, a smaller number of patients with cleft palate was observed, and only our patient had both cleft palate and airway obstruction and was diagnosed with PRS. Previous studies documented that genetically, the specific gene mutations, translocations, deletions, and duplications involving multiple chromosomes related to PRS [1,4,16-19]. This evidence supported that PRS was a disease with genetic heterogeneity. The chromosomal or genetic anomalies were the initiating events of the whole PRS sequence. Therefore, the duplicated 16p13.13-pter region likely led to micrognathia and was also responsible for the PRS phenotype of our patient. At this time, the underlying causes promoting small mandible into PRS are not clarified.Table 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