Search results for " Mutation"
showing 10 items of 1212 documents
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…
High Variability of Fabry Disease Manifestations in an Extended Italian Family
2015
Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolaseα-galactosidase A (α-GAL). The impairment ofα-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male pati…
SPG10 is a rare cause of spastic paraplegia in European families.
2008
Contains fulltext : 71099.pdf (Publisher’s version ) (Closed access) BACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. OBJECTIVE: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype. PATIENTS AND METHODS: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families. RESULTS: Th…
The deletion of six amino acids at the C-terminus of the alpha 1 (II) chain causes overmodification of type II and type XI collagen: further evidence…
1996
We have identified an 18 bp deletion in exon 49 of the type II procollagen gene (COL2A1) in a patient with Kniest dysplasia. The deletion is located at the very C-terminus of the helical domain and removes two of three Gly-Pro-Pro triplets at positions 1007-1012, which are thought to be involved in helix formation and stability. Morphological investigation of an iliac crest biopsy showed large inclusions in the endoplasmic reticulum of chondrocytes, reflecting impaired secretion of type II collagen. Electrophoretic analysis of collagens extracted from cartilage or synthesised by cultured chondrocytes showed that type II and also type XI procollagen molecules containing mutant alpha 1 (II) c…
Deficient membrane integration of the novel p.N14D-GJB2mutant associated with non-syndromic hearing impairment
2006
Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many o…
Nonendodontic periapical lesions: a retrospective descriptive study in a Brazilian population
2021
Background Several nonendodontic diseases can occur in the periapical region, resembling endodontic inflammatory conditions. Therefore, the aim of the present study was to determine the frequency of nonendodontic periapical lesions diagnosed in a Brazilian population. Material and Methods The files of two Oral Pathology laboratories were reviewed and all cases including at least one clinical diagnosis of endodontic periapical lesions were selected for the study. After initial selection, demographic and clinical data, clinical diagnosis and final diagnosis were reviewed and tabulated. Final diagnosis included endodontic periapical lesions, and benign and malignant nonendodontic periapical le…
Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disabilit…
2019
International audience; Purpose Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. Methods Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individu…
Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study
2011
Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. Methods: A total of 16511 HIV-1 reverse transcriptase and protease sequences from 11492 treatment-experienced …
Ulnar ray defect in an infant with a 6q21;7q31.2 translocation: Further evidence for the existence of a limb defect gene in 6q21
1995
Ectrodactyly is a developmental defect of the distal limbs characterized by marked clinical variability and genetic heterogeneity, also reflected in the observation of different chromosome abnormalities non randomly associated with longitudinal postaxial limb deficiencies. The one most frequently found in patients with split hand-split foot (SHSF) involves chromosome band 7q22. Recently, structural anomalies of chromosome 6q21 have been reported in 2 unrelated patients with SHSF, suggesting that this region may also contain genes responsible for limb development [Braverman et al., 1993. Am J Hum Genet, suppl 53: 410; Viljoen and Smart, 1993. Clin Dysmorph 2: 274-277]. We report on a third p…
Two Cases of Thyroid Dysgenesis Caused by Different Novel PAX8 Mutations in the DNA-Binding Region: In Vitro Studies Reveal Different Pathogenic Mech…
2013
Mutations in PAX8, a transcription factor gene, cause thyroid dysgenesis (TD). The extreme variability of the thyroid phenotype makes it difficult to identify individuals harboring PAX8 gene mutations. Here we describe two patients with TD and report two novel PAX8 gene mutations (S54R and R133Q). We performed in vitro studies to functionally characterize these mutations.Using PAX8 expression vectors, we investigated whether the PAX8 mutants localized correctly to the nucleus. To analyze the DNA-binding properties of S54R and R133Q, electrophoretic mobility shift assays were performed. Furthermore, we measured whether the mutant PAX8 proteins were able to activate the thyroglobulin (TG)- an…