Recurrent NEDD4L Variant in Periventricular Nodular Heterotopia, Polymicrogyria and Syndactyly

NEDD4L encodes an ubiquitin ligase which is expressed in the cortex and ventricular zone of the fetal brain. Missense variants in NEDD4L have been reported in nine patients with periventricular nodular heterotopia (PNH), polymicrogyria, cleft palate, and syndactyly. All reported variants are located in the HECT domain, causing deregulation of signaling pathways, including the AKT/mTOR pathway. Here we describe a first familial case with four affected members with a high degree of intra-familial phenotypic variability. Phenotypic features in the proband consisted of severe neurodevelopmental delay, refractory seizures, bilateral PNH, and perisylvian polymicrogyria. The other family members were less severely affected with mild developmental delay and isolated bilateral PNH. All family members had syndactyly. An unrelated patient presented with severe neurodevelopmental delay, seizures, and hypospadias, expanding the phenotypic spectrum. MRI revealed bilateral PNH and perisylvian polymicrogyria. All tested patients carry the recurrent variant c.623G> A, p.(Arg208Gln) in the WW domain of NEDD4L. The variant in the unrelated patient occurred de novo. This is the first report of a NEDD4L variant located in the WW domain which is probably involved in the recognition of substrates for ligation suggesting a loss of function variant.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

Related Links:

CONCLUSIONS: Gene-gene interaction between markers in BMP4 and ARHGAP29 may influence the risk of NSCLO in western Han Chinese population, which might explain the missing heritability for NSCL/P. PMID: 32211112 [PubMed]
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research
AbstractObjectivesTo facilitate the best approach during cleft palate surgery, children are positioned with hyperextension of the neck. Extensive head extension may induce intraoperative cerebral ischemia if collateral flow is insufficient. To evaluate and monitor the effect of cerebral blood flow on cerebral tissue oxygenation, near-infrared spectroscopy has proved to be a valuable method. The aim of this study was to evaluate and quantify whether hyperextension affects the cerebral tissue oxygenation in children during cleft palate surgery.Materials and methodsThis prospective study included children (ASA 1 and 2) under ...
Source: Clinical Oral Investigations - Category: Dentistry Source Type: research
Conclusions: There was a low incidence of MH despite complications after initial palate closure. Our results seem to suggest that age at palate closure, type of cleft palate, and type of surgical technique may not be associated with MH. Additionally, subsequent procedures and complications after primary palatoplasty such as VPI and palatal fistula may not restrict maxillary growth. PMID: 32206667 [PubMed]
Source: Hand Surgery - Category: Surgery Authors: Tags: Maxillofac Plast Reconstr Surg Source Type: research
In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Conclusions: We identified substantial heterogeneity and multiplicity of outcome selection and measurement in published studies. These data will inform the consensus building stage of a core outcome set to inform delirium research in the critically ill.
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Online Review Articles Source Type: research
The cause of maxillary growth restriction in patients with cleft lip and palate remains controversial. While studies have investigated the effects surgical technique and timing have on maxillary growth, few fo...
Source: Maxillofacial Plastic and Reconstructive Surgery - Category: ENT & OMF Authors: Tags: Research Source Type: research
Facial plast Surg 2020; 36: 102-111 DOI: 10.1055/s-0040-1701477Rhinoplasty for cleft lip nasal deformities challenges all cleft surgeons. There is great variability of phenotypical anatomy, but iatrogenic changes and scarring from the previous surgeries add another layer of complexity. Rhinoplasties on a patient with cleft lip–palate are technically and intellectually challenging to master requiring a patient-tailored approach. The shape and structure of the nose are changed to improve both function and aesthetic appearance. In the primary setting, nasoalveolar molding is a form of presurgical infant orthopaedics use...
Source: Facial Plastic Surgery - Category: Cosmetic Surgery Authors: Tags: Original Article Source Type: research
More News: Brain | Cleft Palate | Genetics | Neurology