Search results for "ophthalmia"
showing 10 items of 20 documents
The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma.
2013
Abstract Most patients with BRAFV600-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAFV600-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a “long tail” of new mitogen-activated protein kinase (MAPK) pathway alterations (…
Anophthalmia-Waardenburg syndrome with expanding phenotype: does neural crest play a role?
2007
We describe a child with bilateral anophthalmia, limb anomalies, skin lesions, cerebral malformations, epilepsy, and mental retardation. This patient, according to eponymous classification, should fit into the Anophthalmia-Waardenburg syndrome, although he also presents cutaneous and cerebral manifestations never reported in this syndrome until now. These clinical findings could be explained by the new classification of brain malformations, which takes into account the role of neural crest in Waardenburg syndrome.
ALDH1A3 Mutations Cause Recessive Anophthalmia and Microphthalmia
2013
Anophthalmia and microphthalmia (A/M) are early-eye-development anomalies resulting in absent or small ocular globes, respectively. A/M anomalies occur in syndromic or nonsyndromic forms. They are genetically heterogeneous, some mutations in some genes being responsible for both anophthalmia and microphthalmia. Using a combination of homozygosity mapping, exome sequencing, and Sanger sequencing, we identified homozygosity for one splice-site and two missense mutations in the gene encoding the A3 isoform of the aldehyde dehydrogenase 1 (ALDH1A3) in three consanguineous families segregating A/M with occasional orbital cystic, neurological, and cardiac anomalies. ALDH1A3 is a key enzyme in the…
Sedaghatian congenital lethal metaphyseal chondrodysplasia—observations in a second Iranian family and histopathological studies
1987
In 1980, Sedaghatian described in two brothers and one sister a neonatally lethal disorder associated with slight rhizomelic limb shortness, mild platyspondyly, and severe metaphyseal dysplasia. Here data are presented on another Iranian infant with the Sedaghatian syndrome who died on day 4 and was found to have histologic evidence of severe epimetaphyseal dysplasia. The occurrence in children of both sexes in one instance, born to normal parents who were first cousins, and currently apparent confinement of the disorder to Iranians suggests that the Sedaghatian syndrome is an autosomal recessive trait with high gene frequency in Iranians. This may be a more complexly pleiotropic syndrome t…
Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15.
2019
Abstract N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels…
14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with intellectual disability and bilateral microphthalmia, but without holoprosenc…
2011
Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at least 10 cases involving this region have been described and all patients showed a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated with intellectual disability (ID), bilateral microphthalmia, and coloboma, without cerebral anomalies typical of HPE. Except for ocular defects (i.e., microphthalmia, coloboma) consistent with HPE-type anomalies, the minor facial dysmorphia was not suggestive for HPE and the absence of cerebral anomalies sho…
Plasmalogens in the retina: From occurrence in retinal cell membranes to potential involvement in pathophysiology of retinal diseases
2014
Plasmalogens (Pls) represent a specific subclass of glycerophospholipids characterized by the presence of a vinyl-ether bond at the sn-1 position of glycerol. Pls are quantitatively important in membranes of neuronal tissues, including the brain and the retina, where they can represent until almost two-third of ethanolamine glycerophospholipids. They are considered as reservoirs of polyunsaturated fatty acids as several studies have shown that arachidonic and docosahexaenoic acids are preferentially esterified on Pls when compared to other glycerophospholipids. Reduced levels of Pls were observed in a number of neurodegenerative disorders such as glaucoma, the second leading cause of blindn…
Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics
2013
Objectives Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design Prospective analysis. Patients 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF . When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe …
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
2011
International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney canc…
Regulation of immune response in post-operative endophthalmitis
2011
Regulation of immune response in post-operative endophthalmitis. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)