Search results for "Missense"
showing 10 items of 303 documents
Expanding the phenotype of ASXL3 ‐related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic v…
2021
The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution …
The Clinical Significance of Unknown Sequence Variants in BRCA Genes.
2010
Abstract: Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over …
Mutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
1997
AbstractCleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short stature, and other changes in skeletal patterning and growth. In some families, the phenotype segregates with deletions resulting in heterozygous loss of CBFA1, a member of the runt family of transcription factors. In other families, insertion, deletion, and missense mutations lead to translational stop codons in the DNA binding domain or in the C-terminal transactivating region. In-frame expansion of a polyalanine stretch segregates in an affected family with brachydactyly and minor clinical findings of CCD. We conclude th…
Copy Number Variation and Missense Mutations of the Agouti Signaling Protein (<i>ASIP)</i> Gene in Goat Breeds with Different Coat Colors
2009
In goats, classical genetic studies reported a large number of alleles at the <i>Agouti</i> locus with effects on coat color and pattern distribution. From these early studies, the dominant <i>A</i><sup>Wt</sup> (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat <i>ASIP</i> gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-ri…
Structural mapping of GABRB3 variants reveals genotype-phenotype correlations
2021
AbstractPurposePathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability. In the present study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations.MethodsThrough an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3 and we reviewed previously published cases. All missense variants were mapped onto the 3D structure of the GABRB3 subunit and clinical phenotypes associated with the dif…
Minimum Free Energy Based Evaluation of mRNAs Secondary Structures Constructed by 18 Clinically Significant Exonic Single Nucleotide Polymorphisms (S…
2015
Clinically significant 18 Single Nucleotide Polymorphisms (SNPs) from exon regions of Retinoblastoma gene (RB1) were analyzed to find out the structural variations in mRNAs. Online bioinformatic tools i.e., Vienna RNA, RNAfold were used for secondary structure analysis of mRNAs. Predicted minimum Free Energy Change (MFE) was calculated for mRNAs structures. It has been observed that the average of predicted MFE value from 13 nonsense mutations was higher (0.76 kcal/mol) in comparison to 5 missense mutations. Presumably, 13 nonsense mutations are responsible for Nonsense Mediated mRNA Decay (NMD), therefore, excluded from haplotype analysis. From the statistical analysis all the thermodynami…
Sequence characterization of the melanocortin 1 receptor (MC1R) gene in sheep with different coat colour and identification of the putative e allele …
2010
Abstract Sequence of the melanocortin 1 receptor (MC1R) gene (the Extension locus) was obtained from a panel of 73 animals belonging to 9 Italian sheep breeds or populations (Appenninica, Bergamasca, Comisana, Cornigliese-like, Delle Langhe, Massese, Merinizzata Italiana, Sarda and Valle del Belice) with different coat colours. Evaluation of the identified polymorphisms on this phenotype was reported with in silico predictions and comparative approaches within and across breeds and across species. Five novel single nucleotide polymorphisms (SNPs), organized in three haplotypes, were detected. Another haplotype, including the two missense mutations already described for the ED allele, was id…
PORCNmutations in focal dermal hypoplasia: coping with lethality
2009
The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated…
Wolcott-Rallison Syndrome
2004
Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystemic clinical manifestations. Based on genetic studies of two inbred families, we previously identified the gene responsible for this disorder as EIF2AK3, the pancreatic eukaryotic initiation factor 2α (eIF2α) kinase. Here, we have studied 12 families with WRS, totalling 18 cases. With the exception of one case, all patients carried EIF2AK3 mutations resulting in truncated or missense versions of the protein. Exclusion of EIF2AK3 mutations in…
Molecular basis of mucopolysaccharidosis type II: Mutations in the iduronate-2-sulphatase gene
1993
A number of mutations in the X-chromosomal human iduronate-2-sulphatase gene have now been identified as the primary genetic defect leading to the clinical condition known as Hunter syndrome or mucopolysaccharidosis type II. The mutations that are tabulated include different deletions, splice-site and point mutations. From the group of 319 patients thus far studied by Southern analysis, 14 have a full deletion of the gene and 48 have a partial deletion or other gross rearrangements. All patients with full deletions or gross rearrangements have severe clinical presentations. Twenty-nine different "small" mutations have so far been characterised in a total of 32 patients. These include 4 nons…