Search results for "Mutational analysis"
showing 10 items of 245 documents
A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32
2003
Developmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, and environment, and normal senses. The genetic aetiology of dyslexia is heterogeneous and loci on chromosomes 2, 3, 6, 15, and 18 have been repeatedly linked to it. We have conducted a genome scan with 376 markers in 11 families with 38 dyslexic subjects ascertained in Finland. Linkage of dyslexia to the vicinity of DYX3 on 2p was confirmed with a non-parametric linkage (NPL) score of 2.55 and a lod score of 3.01 for a dominant model, and a novel locus on 7q32 close to the SPCH1 locus was suggested with an NPL score of 2.77. The SPCH1 locus has p…
Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide.
2013
The C9ORF72 Spanish Study Group, et al.
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…
In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy.
2009
Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP. The latest gene to be associated with MFM was FLNC; a p.W2710X mutation in the 24th immunoglobulin-like repeat of filamin C was shown to be the cause of a distinct type of MFM in several German families. We studied an International cohort of 46 patients from 39 families with clinically and myopathologically confirmed MFM, in which DES, CRYAB, MYOT, and ZASP mutations have been excluded. In patients from an unrelated family a 12-nucleotide deletion (c.2997_3008del) in FLNC resulting in a predicted in-frame four-residue deletion (p.Val…
Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma
2006
Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended fa…
PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis.
2001
Abstract The molecular basis of PAH deficiency in the Sicilian population is characterized by a marked heterogeneity, with 44 mutations at a single locus identified by a "gene-scanning" approach and accounting for a detection rate of 91%. The remaining 9% of PAH alleles does not bear mutations in any of the 13 exons and 24 exon/intron junctions. Three mutations IVS10nt-11 G > A, R261Q, and A300S accounted for 30.5%, whereas the remaining mutations were found at relative frequencies of less than 5% and 20 mutations were observed once only. Five mutations have been detected only in Sicilians so far. By studying the association of mutations with intragenic STR-VNTR haplotypes ("minihaplotypes"…
A novel mutation of gene CBFA1/RUNX2 in cleidocranial dysplasia.
2007
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells into osteoblasts and is essential for membranous as well as endochondral bone formation. In this study of a 14-yr-old boy with typical CCD phenotype, the authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segment…