Search results for "genetic disease"
showing 10 items of 64 documents
IC3D Classification of Corneal Dystrophies—Edition 2
2015
To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information.The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added.On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial d…
A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome
2016
Using targeted next generation sequencing, we have identified a splicing mutation (c.526-9_526-5del) in the SLC9A6 gene in a 9-year-old boy with mild intellectual disability (ID), microcephaly, and social interaction disabilities. This intronic microdeletion leads to the skipping of exon 3 and to an in-frame deletion of 26 amino acids in the TM4 domain. It segregates with cognitive impairment or learning difficulties in other members of the family. Mutations in SLC9A6 have been reported in X-linked Christianson syndrome associating severe to profound intellectual deficiency and an Angelman-like phenotype with microcephaly, absent speech, ataxia with progressive cerebellar atrophy, ophthalmo…
Amelioration of the abnormal phenotype of a new L1 syndrome mouse mutation with L1 mimetics
2021
L1 syndrome is a rare developmental disorder characterized by hydrocephalus of varying severity, intellectual deficits, spasticity of the legs, and adducted thumbs. Therapy is limited to symptomatic relief. Numerous gene mutations in the L1 cell adhesion molecule (L1CAM, hereafter abbreviated L1) were identified in L1 syndrome patients, and those affecting the extracellular domain of this transmembrane type 1 glycoprotein show the most severe phenotypes. Previously analyzed rodent models of the L1 syndrome focused on L1-deficient animals or mouse mutants with abrogated cell surface expression of L1, making it difficult to test L1 function-triggering mimetic compounds with potential therapeu…
Laboratory investigations in genetic syndromes: examples of clinical approach in the neonatal unit.
2010
Contiguous gene deletion syndromes: the importance of an accurate genetic definition for a careful clinical monitoring. Contiguous gene deletion syndromes are so named because the deletion manifests as a distinctive cluster of otherwise unrelated single-gene disorders in the same subject. An accurate genetic definition of the deleted region is extremely important for the appropriate management of these patients and for unravelling the function of the involved genes. The microarray-based comparative genomic hybridization (CGH arrays) analysis is the actual molecular method able to accurately define the bounds of a deleted region, since it allows an evaluation of DNA copy number alterations a…
X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
2017
By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-li…
Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness.
2015
Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease-causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SL…
Noninvasive assessment of respiratory muscle strength and activity in Myotonic dystrophy
2017
Objective To evaluate sensitivity/specificity of the maximum relaxation rate (MRR) of inspiratory muscles, amplitude of electromyographic activity of the sternocleidomastoid (SCM), scalene (SCA), parasternal (2ndIS) and rectus abdominis (RA) muscles; lung function and respiratory muscle strength in subjects with Myotonic dystrophy type 1 (DM1) compared with healthy subjects. Design and methods Quasi-experimental observational study with control group. MRR of inspiratory muscles, lung function and amplitude of the electromyographic activity of SCM, SCA, 2ndIS and RA muscles during maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) and sniff nasal inspiratory pressure (…
Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.
2014
The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome with marked clinical variability and incomplete penetrance. The average size of the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has been identified as the gene responsible for the neurological phenotype in this microdeletion syndrome. Only seven patients with a homozygous microdeletion that includes at least CHRNA7, and is inherited from both parents have been described in the literature. The aim of this study was to further describe the distinctive eye manifestations from the analysis in the three French patients diagnosed with the classical 1.5 Mb homozygous microdeletion. Patients…
"I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.
2016
Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in th…
Results of mitral valve repair for Barlow disease (bileaflet prolapse) via right minithoracotomy versus conventional median sternotomy: a randomized …
2011
Objective: The results of mitral repair for complex Barlow valves are adequate and support earlier intervention. It is unknown whether these results are reproducible in the context of minimally invasive surgery via right minithoracotomy. Methods: We randomized patients with Barlow mitral disease (bileaflet prolapse) to have conventional open repair via median sternotomy (MS group) or minimally invasive (MI group) repair. Repair was done using polytetrafluoroethylene chordal reimplantation for both leaflets. In the MI group, we adopted right minithoracotomy, peripheral cannulation, external aortic clamping, and surgery under direct vision. Results: Both groups comprised 70 patients. The oper…