Confirmation of Nablus mask‐like facial syndrome

Salpietro, Carmelo; Briuglia, Silvana; Rigoli, Luciana; Merlino, Maria; Dallapiccola, Bruno

doi:10.1002/ajmg.a.20280

Cited by 18 publications

(20 citation statements)

References 2 publications

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“…GDF6 mutations in humans have been associated with eye and postcranial skeletal abnormalities although these effects are characterized by incomplete penetrance and phenotypic heterogeneity [15], [32]. Interestingly, genomic lesions close to the GDF6 genomic region are associated with Nablus Mask-Like Facial Syndrome [33], [34], [35] which is a complex multigene deletion syndrome characterized by loss of a critical region just proximal to GDF6 . In one of only two known patients where the genomic deletion included GDF6 , coronal craniosynostosis was observed [33], [34].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, genomic lesions close to the GDF6 genomic region are associated with Nablus Mask-Like Facial Syndrome [33], [34], [35] which is a complex multigene deletion syndrome characterized by loss of a critical region just proximal to GDF6 . In one of only two known patients where the genomic deletion included GDF6 , coronal craniosynostosis was observed [33], [34]. We propose that some individuals having coronal craniosynostosis with unknown etiology may harbor mutations in GDF6 .…”

Section: Discussionmentioning

confidence: 99%

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The BMP Ligand Gdf6 Prevents Differentiation of Coronal Suture Mesenchyme in Early Cranial Development

Clendenning

Mortlock

2012

PLoS ONE

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Growth Differentiation Factor-6 (Gdf6) is a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules. Previous studies have shown that Gdf6 plays a role in formation of a diverse subset of skeletal joints. In mice, loss of Gdf6 results in fusion of the coronal suture, the intramembranous joint that separates the frontal and parietal bones. Although the role of GDFs in the development of cartilaginous limb joints has been studied, limb joints are developmentally quite distinct from cranial sutures and how Gdf6 controls suture formation has remained unclear. In this study we show that coronal suture fusion in the Gdf6−/− mouse is due to accelerated differentiation of suture mesenchyme, prior to the onset of calvarial ossification. Gdf6 is expressed in the mouse frontal bone primordia from embryonic day (E) 10.5 through 12.5. In the Gdf6−/− embryo, the coronal suture fuses prematurely and concurrently with the initiation of osteogenesis in the cranial bones. Alkaline phosphatase (ALP) activity and Runx2 expression assays both showed that the suture width is reduced in Gdf6+/− embryos and is completely absent in Gdf6−/− embryos by E12.5. ALP activity is also increased in the suture mesenchyme of Gdf6+/− embryos compared to wild-type. This suggests Gdf6 delays differentiation of the mesenchyme occupying the suture, prior to the onset of ossification. Therefore, although BMPs are known to promote bone formation, Gdf6 plays an inhibitory role to prevent the osteogenic differentiation of the coronal suture mesenchyme.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The BMP Ligand Gdf6 Prevents Differentiation of Coronal Suture Mesenchyme in Early Cranial Development

Clendenning

Mortlock

2012

PLoS ONE

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“…2a-c) is a girl with a facial appearance similar to Patient 1, including tight and glistening facial skin, blepharophimosis, short palpebral fissures, distinctive ears, and dental anomalies. She was previously reported on [Salpietro et al, 2003]; however a genetic cause for her pattern of malformation was not identified at that time. Follow-up evaluation at 5 years and 2 months of age (Fig.…”

Section: Clinical Evaluationmentioning

confidence: 76%

“…He also demonstrates camptodactyly, contractures, unusual dentition, cryptorchidism, mild developmental delay, and a happy demeanor. Patient 2, a girl with a strikingly similar phenotype, was previously described in a report by Salpietro et al [2003]. She has distinctive ears, dental anomalies, and developmental delay.…”

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confidence: 72%

Nablus mask‐like facial syndrome is caused by a microdeletion of 8q detected by array‐based comparative genomic hybridization

Shieh

Aradhya

Novelli³

et al. 2006

American J of Med Genetics Pt A

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In 2000, Teebi reported on a 4-year-old boy with a distinctive pattern of malformation, which he termed the "Nablus mask-like facial syndrome" (OMIM# 608156). Characterization of this syndrome has been difficult because of the paucity of patients described in the medical literature and its unknown etiology and pathogenesis. We present two patients with Nablus mask-like facial syndrome who both display a microdeletion in the 8q21-8q22 region detected by array-based comparative genomic hybridization. Patient 1, a boy, has a distinct facial appearance characterized by severe blepharophimosis, tight-appearing glistening facial skin, sparse and unruly hair, a flat and broad nose, and distinctive ears that are triangular in shape with prominent antihelices. He also demonstrates camptodactyly, contractures, unusual dentition, cryptorchidism, mild developmental delay, and a happy demeanor. Patient 2, a girl with a strikingly similar phenotype, was previously described in a report by Salpietro et al. 2003. She has distinctive ears, dental anomalies, and developmental delay. The etiology of her pattern of malformation was not identified at that time. Although high-resolution chromosome and subtelomeric FISH analyses were normal, array-based comparative genomic hybridization revealed an approximately 4 Mb deletion involving the 8q21.3-8q22.1 region in both patients. This region encompasses a number of genes that may contribute to this unique phenotype. These results demonstrate a chromosomal microdeletion as the etiology of Nablus mask-like facial syndrome and emphasize the diagnostic utility of array-based comparative genomic hybridization in the evaluation of multiple malformation syndromes of previously unrecognized causation.

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“…It is defined by distinctive facial appearance, including blepharophimosis, tight appearing glistening facial skin, a flat and broad nose, distinctive ears, and abnormal hair pattern. Children have happy behavior and moderate developmental delay [Salpietro et al, 2003]. Microdeletions in 8q21.3-8q22.1 regions have been found in all four patients by array comparative genome hybridization (aCGH).…”

Section: Introductionmentioning

confidence: 97%

A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask‐like facial syndrome

Debost‐Legrand¹,

Eymard-Pierre

Pebrel‐Richard

et al. 2012

American J of Med Genetics Pt A

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Microdeletions of 8q21.3-8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3-8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS.

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Confirmation of Nablus mask‐like facial syndrome

Cited by 18 publications

References 2 publications

The BMP Ligand Gdf6 Prevents Differentiation of Coronal Suture Mesenchyme in Early Cranial Development

The BMP Ligand Gdf6 Prevents Differentiation of Coronal Suture Mesenchyme in Early Cranial Development

Nablus mask‐like facial syndrome is caused by a microdeletion of 8q detected by array‐based comparative genomic hybridization

A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask‐like facial syndrome

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